Persistence Market Research (PMR) has published a new research report on canine stem cell therapy. The report has been titled, Canine Stem Cell Therapy Market: Global Industry Analysis 2016 and Forecast 20172026.Veterinary research has been used in regenerative and adult stem cell therapy andhas gained significant traction over the last decade. Canine stem cell therapy products are identified to have gained prominence over the past five years, and according to the aforementioned research report, the market for canine stem cell therapy will expand at a moderate pace over the next few years.

Though all animal stem cells are not approved by FDA, veterinary stem-cell manufacturers and university researchers have been adopting various strategies in order to meet regulatory approvals, and streamline and expedite the review-and-approval process. The vendors in the market are incessantly concentrating on research and development to come up with advanced therapy, in addition to acquiring patents.

In September 2017, VetStem Biopharma, Inc. received European patent granted to the University of Pittsburgh and VetStem received full license of the patent then. This patent will eventually provide the coverage for the ongoing commercial and product development programs of VetStem and might be also available for licensing to other companies who are rather interested in this field. The other companies operating in the global market for canine stem cell therapy are VETherapy Corporation, Aratana Therapeutics, Inc., Regeneus Ltd, Magellan Stem Cells, Animal Cell Therapies, Inc., and Medrego, among others.

According to the Persistence Market Research report, the globalcanine stem cell therapy marketis expected to witness a CAGR of 4.2% during the forecast period 2017-2026. In 2017, the market was valued at US$ 151.4 Mn and is expected to rise to a valuation of US$ 218.2 Mn by the end of 2026.

Burgeoning Prevalence of Chronic Diseases in Dogs to Benefit Market

Adipose Stem Cells (ASCs) are the most prevalent and in-demand adult stem cells owing to their safety profile, ease of harvest, and use and the ability to distinguish into multiple cell lineages. Most early clinical research is focused on adipose stem cells to treat various chronic diseases such as arthritis, tendonitis, lameness, and atopic dermatitis in dogs. A large area of focus in veterinary medicine is treatment of osteoarthritis in dogs, which becomes more prevalent with age. Globally, more than 20% dogs are suffering from arthritis, which is a common form of canine joint and musculoskeletal disease. Out of those 20%, merely 5% seem to receive the treatment. However, elbow dysplasia in canine registered a prevalence rate of 64%, converting it into an alarming disease condition to be treated on priority. Thereby, with the growing chronic disorders in canine, the demand for stem cell therapy is increasing at a significant pace.

Expensive Nature of Therapy to Obstruct Growth Trajectory

Expensive nature and limited access to canine stem cell therapy has demonstrated to be a chief hindrance forestalling its widespread adoption. The average tier II and tier III veterinary hospitals lack the facilities and expertise to perform stem cell procedures, which necessitates the referral to a specialty vet hospital with expertise veterinarians. A trained veterinary physician charges high treatment cost associated with stem cell therapy for dogs. Generally, dog owners have pet insurance that typically covers maximum cost associated with steam cell therapy to treat the initial injury but for the succeeding measures in case of retreatment, the costs are not covered under the pet insurance. The stem cell therapy is thus cost-prohibitive for a large number of pet owners, which highlights a major restraint to the market growth. Stem cell therapy is still in its developmental stage and a positive growth outcome for the market cannot be confirmed yet.

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Canine Stem Cell Therapy Market is Anticipated to Register Highest CAGR of 4.2% Throughout the Forecast Quantity 2017-2026 - Statsflash

HE PUT A camera in a carcass and waited for the wolves to come.

That, says Whitney Johnson, director of visuals and immersive experiences, is the kind of effort that makes for a standout National Geographic photo.

How does she choose 100 photos from 106 photographers, 121 stories, and more than two million images taken over the course of a year?

I count on my great photo editors, says Johnson.

One of her favourite images is the lead photo of the Mona Lisa because it reflects what Johnson calls the magic of what makes photography hardshowing something familiar in a new way. It also speaks to what happens behind the scenesthe photo editor getting access while the museum was closedand behind the lens, that charmed combination of luck, accident, and a photographer really seeing the moment.

There are many such moments here, from military exercises in a warming Arctic and Rwandan schoolgirls flexing their muscles to Alex Honnold climbing El Capitans sheer face without ropes. Johnson calls that particular photo run a whole stretch of strength across space and time.

With Californias Yosemite Valley far beneath him, Alex Honnold free soloswhich means climbing without ropes or safety gearup a crack on the 914-metre southwest face of El Capitan. Before he accomplished the feat on June 3, 2017, Honnold spent nearly a decade thinking about the climb and more than a year and a half planning and training for it.PHOTOGRAPH BY JIMMY CHIN

Time is reflected in other ways too. Theres the frozen body of Susan Potter, a woman determined to donate her body to medical education, a story carefully shepherded for 17 years by photo editor Kurt Mutchler. And theres the heartbreaking photo of Sudan, the last male northern white rhinoceros, as he lay dying.

But there is also so much joy: captive songbirds released to the sky and Japans obsession with all things kawaii (cute and cuddly). And so much strangeness.

The image that speaks most to me is that of an orphaned young giraffe, its long neck draped over its human caregiver in what looks to be a loving hug. The giraffe now runs free with a wild herd. When exploring these pictures, we all might hear from our own internal photo editor, the voice inside us that tells us to pause, asking us to take a closer look.

An orphaned giraffe nuzzles a caregiver at Sarara Camp in northern Kenya. Samburu cattle herders found the abandoned calf and alerted Sararaknown for raising orphaned mammals and returning them to their habitat. The young giraffe now lives with a wild herd.PHOTOGRAPH BY AMI VITALE

Petronella Chigumbura, a member of the Akashingaa nonprofit, all-female anti-poaching unitpractices reconnaissance techniques in the Zimbabwean bush.PHOTOGRAPH BY BRENT STIRTON

A male elephant grabs an evening snack in Mozambiques Gorongosa National Park. Most of the parks elephants were killed for their ivory, used to buy weapons during the nations 15-year civil war, which ended in 1992. With poaching controlled, the population is recovering.PHOTOGRAPH BY CHARLIE HAMILTON JAMES

Issa Diakite, 50, built both his barbell and his home, one of dozens of chabolas clustered near an Andalusian agricultural region in Spain. Originally from Mali, he settled in as a regular fieldworker and now helps other migrants build shacks.PHOTOGRAPH BY AITOR LARA

Cynthia Ikirezi (centre) beams with her fellow prefects, student leaders, at Gashora Girls Academy in Rwanda. Educating girls and preparing them for leadership roles are government priorities to empower women.PHOTOGRAPH BY YAGAZIE EMEZI

Marines have to be able to carry one another if necessary. USMC Cpl. Gabrielle Green hefts a fellow marine as they ready for deployment on a Navy ship at Camp Lejeune, North Carolina. Of the 38,000 recruits who enter the corps each year, about 3,500 are womenor, in USMC phrasing, female marines.PHOTOGRAPH BY LYNSEY ADDARIO

Encased in polyvinyl alcohol, Susan Potters body awaits freezing after she donated her body to science. It was frozen, sawed into four blocks, sliced 27,000 times, and photographed after each cut. The result: a virtual cadaver that will speak to medical students from the grave.PHOTOGRAPH BY LYNN JOHNSON

Canadian soldiers climb on the wreckage of a plane, roughly 1600 kilometres south of the North Pole, to scout the area during an Arctic survival course on Cornwallis Island. As the Arctic warms and tensions over its future rise, the Canadian and U.S. militaries have stepped up operations in the region.PHOTOGRAPH BY LOUIE PALUPHOTOGRAPHY FOR THIS ARTICLE WAS SUPPORTED BY GRANTS FROM THE JOHN SIMON GUGGENHEIM MEMORIAL FOUNDATION AND THE PULITZER CENTER.

Some 400 U.S. soldiers practice parachute jumps near Alaskas Fort Greely. The multinational exercise, which includes Canadian forces, prepares troops for the rigors of large, coordinated operations in extreme cold conditions.PHOTOGRAPH BY LOUIE PALUPHOTOGRAPHY FOR THIS ARTICLE WAS SUPPORTED BY GRANTS FROM THE JOHN SIMON GUGGENHEIM MEMORIAL FOUNDATION AND THE PULITZER CENTER.

Canadian soldiers build an igloo during the high Arctic phase of their training to become Arctic operations advisers. In this part of the program, they learn to travel, survive, and build shelters when they reach the high Arctic.PHOTOGRAPH BY LOUIE PALUPHOTOGRAPHY FOR THIS ARTICLE WAS SUPPORTED BY GRANTS FROM THE JOHN SIMON GUGGENHEIM MEMORIAL FOUNDATION AND THE PULITZER CENTER.

Buyers choose animals at the livestock market and send them to this slaughterhouse in Agadez, Niger, where camels, goats, sheep, and other animals are killed and then sent to butchers who sell the meat.PHOTOGRAPH BY PASCAL MAITRE

In Agadez, Niger, an Izala school educates about 1,300 students. Izala is a back-to-basics Islamic reformist movement that adheres to conservative practices, such as women covering their faces, but also prizes education.PHOTOGRAPH BY PASCAL MAITRE

A teenager is dusted with sand from toiling in a mine. He is one of many Nigeriens who joined the rush for gold in the north, the last hope for jobless men after tourism plunged, uranium mining declined, and a law made transporting migrants a crime.PHOTOGRAPH BY PASCAL MAITRE

Stuck in the desert beyond Agadez, Niger, after their truck broke down, these migrants who are hoping to make it to Libya burn a tire to keep warm.PHOTOGRAPH BY PASCAL MAITRE

Kurdish fighters surround a surrendering woman as ISIS abandons the town of Baghouz, Syria in March. Women who joined or were forced into ISIS need guidance away from an oppressive version of Islam, a Kurdish female fighter says. They understand the religion in the wrong way.PHOTOGRAPH BY LYNSEY ADDARIO

Knight Mai (left) and Florence Stima (right), who are South Sudanese, work at a salon in Uganda's Bidibidi refugee camp. Each makes less than five dollars a week. Small businesses have filled out market areas, but few private companies have tapped into the labour potential of the camp.PHOTOGRAPH BY NORA LOREK

In Tinun, Mexico, Beatriz, 18, combs her son Andrs hair after a bath. Beatriz is a beekeeper and learned the craft from her grandfather Anastacio Balan Osalde, who passed away two days earlier.PHOTOGRAPH BY NADIA SHIRA COHEN

Feeling dizzy and weak six months after giving birth, Zamzam Yousuf, 35, came into a clinic in the village of Habasweyn in Somaliland run by the Edna Adan University Hospital. Her blood pressure was extremely high. Yousuf was treated by student midwife Farduus Mubarak, 22, under the watchful eye of the hospitals founder, Edna Adan Ismail, 81.PHOTOGRAPH BY LYNSEY ADDARIO

Aisha Barka and her daughter, Mariam, hadnt eaten in days when they arrived in an Eritrean refugee camp in 2008, driven from their home by drought, which killed all their animals. After the Eritrean military began abducting young men, people fled for safety across the border into Ethiopia.PHOTOGRAPH BY JOHN STANMEYER

Children nap at a kindergarten in Mongolias Bayanzurkh District. Each room is equipped with an air purifier, in an attempt to lower the level of indoor air pollution. Children are especially vulnerable to poor air quality.PHOTOGRAPH BY MATTHIEU PALEY

Pedestrians, shoppers, and people-watchers stroll on Chuo-dori in Ginza, one of Tokyos busiest destinations. Cars travel on the street during weekdays, but on weekend afternoons a one-mile strip is closed to traffic and becomes a promenade. Cafs, high-end boutiques, and street performers attract local residents and visitors.PHOTOGRAPH BY DAVID GUTTENFELDER

Young men from Niger and elsewhere wait in a migrant ghetto in Agadez, Niger, for a caravan to Libya. With low life expectancy, limited educational opportunities, and a high poverty rate, Niger ranks at the bottom of the UNs Human Development Index.PHOTOGRAPH BY PASCAL MAITRE

Sal Thegal dressed like a hot dog at the Minnesota State Fair on Friday, August 23, 2019.PHOTOGRAPH BY ACKERMAN + GRUBER

Jorge Castellon, an employee at the Saguaro Hotel in Palm Springs, California, poses with a fan (used for dancing) in May 2019. When not working at the Saguaro, Castellon is a professional dancer and dance instructor. Palm Springs is like a paradiseits heaven on earth, says Castellon. The people who come here are unique and visit with a purpose, to have fun. Were just here to play!PHOTOGRAPH BY JENNIFER EMERLING

Patricia Frazier carries the flag of Benin, the modern nation once ruled by the king of Dahomey, who sold 110 captives to the captain of the Clotildathe last known ship to bring enslaved Africans to American shores. If they find that ship, I think it will make people more aware of our history, says Frazier before the vessel was found. Sometimes you need something tangible to spur those memories.PHOTOGRAPH BY ELIAS WILLIAMS

Malaysia, 40, poses for a story about the Stonewall riots of 1969 that sparked riots and 50 years of a national LGBTQ civil rights movement. In life things tend to show you not your wants but your needs. And, transitioning into Malaysia ... has opened up a world of acceptance for me. Because now I am comfortable, and I've never been this comfortable in my life.PHOTOGRAPH BY ROBIN HAMMOND

Joseph Wachira, a keeper at the Ol Pejeta Conservancy in Kenya, says goodbye to Sudan, the last male northern white rhinoceros. Sudan died in 2018. Two females of the subspecies remain.PHOTOGRAPH BY AMI VITALE

A hunter from a village in Indonesia says he delivers pangolins to the city of Surabaya on a weekly basis. Pangolins are protected by national laws in the countries where theyre found, and international commercial trade in them is banned. Even so, poaching and trafficking are major threats to pangolins survival.PHOTOGRAPH BY BRENT STIRTON

A Temmincks ground pangolin named Tamuda searches for a meal of ants or termites at a rehabilitation center in Zimbabwe. He was rescued from illegal wildlife traders, who likely would have smuggled his scales to Asia for use in traditional remedies.PHOTOGRAPH BY BRENT STIRTON

Late in the dry season, a remnant pool in the Mussicadzi River channel attracts a mob of hungry birds, including storks, egrets, and hammerkops, along with a couple of thirsty waterbuck in Mozambique's Gorongosa National Park. Gorongosas avian richness swells further in the wet season, when nomads arrive to feed.PHOTOGRAPH BY CHARLIE HAMILTON JAMES

A crocodile rests in Mozambiques Gorongosa National Park, where wildlifes future depends on humans livelihoods.PHOTOGRAPH BY CHARLIE HAMILTON JAMES

Once or twice a month during Costa Ricas rainy season, female olive ridley sea turtles come ashore by the tens of thousands and lay eggs in a mass nesting event known as an arribada. Hatchlings begin emerging about 45 days later.PHOTOGRAPH BY THOMAS P. PESCHAK

Wolves in the Canadian Arctic pick at the remains of a muskox. To get this image, photographer Ronan Donovan placed a camera trap inside the carcass. The pack returned to feed on and off for a month.PHOTOGRAPH BY RONAN DONOVAN

All clear? A New York City rat peeks out from a stormwater catch basin.PHOTOGRAPH BY CHARLIE HAMILTON JAMES

Two rats at India's Karni Mata Temple box to determine which is dominant. Rats are social animals that take good care of their offspring. Studies show they will free a fellow rat from a small cageeven if it means giving up a treat. This suggests to some researchers that rats feel empathy.PHOTOGRAPH BY CHARLIE HAMILTON JAMES

Behind netting, a polar bear dances at the Circus on Ice in Kazan, Russia. Performing polar bears are extremely rare. The shows four bears wear metal muzzles, and their trainer, Yulia Denisenko, carries a metal rod. Between tricks, the bears lie down and rub themselves on the ice.PHOTOGRAPH BY KIRSTEN LUCE

Confiscated songbirds that were seized from illegal owners are released after weeks in a rehab aviary where they strengthened their wings and learned to fly again.PHOTOGRAPH BY KARINE AIGNER

Inmates at the San Francisco Gotera prison who have renounced their gang ties pray together. Prison-based evangelical churches in El Salvador are growing.PHOTOGRAPH BY MOISES SAMAN

Thousands of migratory songbirds are caught around Florida each year to supply a thriving illegal market. Before seized birds are released back into the wild by law enforcement, they are put in an aviary for several weeks where they learn how to fly again as well as how to find new food.PHOTOGRAPH BY KARINE AIGNER

Clay, Daniel, and Enzo, three of 39 tigers rescued from an animal park in Oklahoma, gather at a pool at the Wild Animal Sanctuary in Keenesburg, Colorado. These cats will live out their lives here, with proper nutrition and vet care.PHOTOGRAPH BY STEVE WINTER

Nine of 24 lions are darted and flown from Tembe and Mkuze game reserves in Kwazulu Natal, South Africa, to Mozambique in June 2018. The wild lions will be released into the Zambeze Delta there. The move is the largest conservation transport of wild lions across an international boundary in history. A hundred years ago, there were over 200,000 wild lions living in Africa.PHOTOGRAPH BY AMI VITALE

Lions that were released and collared in a remote region of the 4,500-square-kilometer Zambeze Delta area of Mozambique lounge in the early morning mist. Mozambiques wildlife was decimated by the countrys civil war and subsequent poaching in the past 20 years. Today, leading researchers estimate Africa's lion population to be 20,000 or less, with lions now extinct in 26 African countries. Mozambique's ecosystem has made a remarkable recoveryexcept for its lions.PHOTOGRAPH BY AMI VITALE

Shadows form over the Deser-est Motor Lodge in Ely, Nevada. Before it was known as the Loneliest Road in America, Route 50 was a thruway during the 1850s gold rush.PHOTOGRAPH BY MATHIAS SVOLD

In northwestern Colombia, hunters have long employed their own form of camouflage: masks made of broad, sturdy leaves known as hojancha. These masks are used in order to sneak up on turtles and other game animals such as wading and migratory birds. Hunting is still a vital activity for subsistence farmers in the region.PHOTOGRAPH BY GENA STEFFENS

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The Best Photos Of 2019 | Australia | National Geographic - National Geographic Australia

The mother of a cancer survivor has released a heartbreaking photograph to show the reality of the disease.

Sophia Soto, from Florida, was diagnosed with stage four neuroblastoma at just 14 months old after unusual bruises developed around her eyes.

READ MORE:Girl with neuroblastoma declared cancer-free after pioneering treatment

With doctors dismissing it as just a fall, an eye specialist eventually found tumours behind her eyes were to blame.

The toddler endured 60 rounds of chemo, 20 of radiotherapy and a stem cell transplant over six months. She was snapped just before having treatment.

Sophia, now six, has been in remission for five years and medication-free for the past 24 months.

Now six, Sophia has been off medication for the past two years. [Photo: Caters]

Speaking of her daughters condition, Sophias mother Rosie Soto, 40, said: The picture of Sophia upset really does hone in on the reality of childhood cancer.

She was having a lead put on her chest for her treatment, which she didn't want, hence why Sophia was so upset.

I look back at the picture now and wonder how I did it. It was so hard watching my little girl so ill.

Neuroblastoma is a rare type of cancer that mainly affects babies and young children,according to the NHS.

READ MORE:Childhood Cancer Survivors Are Twice as Likely to Have This Condition

Around 95 youngsters in the UK are diagnosed every year, making up 6% of all childhood-cancer cases,Children with Cancer UK statistics show.

In the US, around 800 are diagnosed annually, also accounting for 6% of all cases,according to the American Cancer Society.

Neuroblastoma develops in specialised nerve cells called neuroblasts, which get left behind during a babys development in the womb.

The disease tends to start in one of the adrenal glands above the kidneys or nerve tissue next to the spinal cord, before spreading.

Sophia's parents Javier and Rosie Soto watched her battle the disease. [Photo: Caters]

Mrs Soto became concerned when her daughter develop bruises around her eyes, with no obvious cause.

I kept taking her to the doctors because the bruising wasn't going away, but they just said it must have been from a bump or something, she said.

Sophia wasn't referred for a scan or biopsy until I went to an eye specialist, who knew straight away it was caused by a tumour.

She was sent for an MRI, where black spots appeared on the scans confirmed the tumours behind her eyes.

[A] biopsy found tumours on one of her kidneys as well, which led to her stage four neuroblastoma diagnosis.

Sophia discovered she had the disease in March 2014, aged just 14 months.

After extensive treatment, the youngster has been in remission since that November, but still has check-ups every six months.

The tumours behind her eyes cannot be removed, however, doctors believe they are now benign.

READ MORE: Mom beats breast cancer and then books 'dream' trip

Doctors are reluctant to remove the tumours Sophia has behind her eyes as they've said it would be likely the surgery [would] disfigure her face, Mrs Soto said.

Whilst they are tumours, doctors are reasonably confident they are not cancerous so we have decided to not have the surgery right now, but it may be something she has when she's older.

Over the worst, Sophia loves dancing and dreams of one day becoming a vet.

No one can imagine what she went through looking at her now, she just looks like a normal regular child, Mrs Soto said.

Sophia has her moments when she asks about when she was sick and has questions about her treatment scars, but overall she's a pretty happy girl.

If I was to say anything to other parents with children battling cancer, I'd say to not give up, stay positive.

It's really important not to compare your child's process to anyone else as everyone battles illnesses differently.

We're over the moon Sophia is now doing so well. We're really blessed she's such a fighter.

Originally posted here:
Heartbreaking photograph shows the reality of childhood cancer - Yahoo Lifestyle

The current Stem Cells Cryopreservation Equipments market research report has demonstrated all the vital market growth factors and economic fluctuations mentioned owing to the vast attention gained in recent years.

The Stem Cell Cartilage Regeneration market report provides a meticulous picture of the sector by summary of data, production, and method of study originated from various sources.

The high numbers of specialized veterinarians and veterinary clinics in these regions also contribute to the promising growth opportunities held by the canine stem cell therapy market in these regions. The market is growing with technological innovation, competition and M&A activities in the industry are offering specific application products for varied end-users.

The report is a thorough analysis of the Autologous Stem Cell and Non-Stem Cell Based Therapies Market.

Stem cell assay refers to the procedure of measuring the potency of antineoplastic drugs, on the basis of their capability of retarding the growth of human tumor cells. In-depth analysis of numerous components has been studied in the report including supply and demand Figures, cost, price, revenue, gross margins, current geographical zones, technology, demand-supply and consumption. Comprising an in-depth analysis of the various factors boosting and inhibiting the growth of the market, this report is a key to making profitable decisions by investing in the correct segment and sub-segment, which is anticipated to make the most progress in the future.

The report analyzes the prevalent opportunities for the market's growth and those that companies should capitalize in the near future to strengthen their position in the market.

Common sense to rest Man United seniors for Astana trip: SolskjaerA statement released by the club In February said "everybody looks forward to seeing him wear the red shirt again". Their last outing against Sheffield United ended in 3-3 draw and they surely don't repeat that feat this time.

Global Market portal aims to provide reports like these in order to draw the attention of numerous clients wanting to extrapolate some of the vital details of the Stem Cells Cryopreservation Equipments market on a global scale. The report provides an extensive evaluation of each market segment considering its demand, production, sales revenue, and potential growth. The solid research on the Animal Stem Cell Therapy Market is prepared with the aim to meet the requirements of the customer in terms of the availability of data, analytics, statistics, and an accurate forecast market.The market report also presents the landscape and a corresponding detailed analysis of the major players operating in the market. The ones holding the most lucrative prospects are analyzed, and the factors restraining its trajectory across key segments are also discussed at length. USA, Europe, Japan, China, India, Southeast Asia, South America, South Africa, Others. By kit, the market can be bifurcated into human embryonic stem cell kits and adult stem cell kits.

- Which Trending factors influencing the market shares of the top regions across the globe?

- Who are the key market players and what are their strategies in the global Animal Stem Cell Therapy market? Moreover, studies showing the excellent level of safety granted by allogeneic stem cell therapy are also rising in numbers, leading to increased confidence among pet owners as well as veterinarians regarding canine stem cell therapy.

- What industrial trends, drivers and challenges are manipulating its growth?

- What are the key outcomes of the five forces analysis of the global Animal Stem Cell Therapy market? The clients and other readers can have all the global Stem Cells Cryopreservation Equipments market highlights provided in this very report. It also conducts SWOT analysis to study the strengths and weaknesses of the companies profiled and identify threats and opportunities that these enterprises are forecast to witness over the course of the report's forecast period. The increasing incidence of chronic ailments and the subsequently expanding patient population are the chief drivers of the stem cell assay market in North America. The report has all the vital information regarding supply and demand, market development enhancers, market share, sales distributors, and more advocated in a very formal pattern.

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Canine Stem Cell Therapy Market Value Projected to Expand by 2026 - The Hilltop Monitor

27 Nov 2019

Twenty years ago, researchers took fibroblasts from the skin of eight Alzheimers patients, engineered them to produce nerve-growth factor, and slid them into each volunteers basal forebrain. They hoped the neurotrophin would halt or slow the neurodegeneration that robbed them of their memories, indeed their lives. The gamble failed and since then, scientists have shown little zest for gene therapy in neurodegenerative disorders. That is changing. As evident at this years Society for Neuroscience conference, held October 1923 in Chicago, gene therapy is back. Buoyed by success in treating spinal muscular atrophy in infants, scientists are flush with new ideasand funding.

What was once considered risky, expensive, and unlikely to succeed is now seen by many as risky, expensiveand quite likely to succeed. A growing number of scientists think gene-based therapies may have the best chance of slowing, or even preventing, neurodegeneration, especially for disorders caused by mutations in a single gene. SfN hosted a press briefing on gene therapy, plus many projects are active throughout the field beyond those showcased at the conference. There was no breaking clinical trial news at the annual meeting, but the scope and challenges of such therapies were outlined at the briefing moderated by Rush University s Jeff Kordower, Chicago, as well as a translational roundtable moderated by Asa Abeliovich, Columbia University, New York. Abeliovich recently co-founded Prevail Therapeutics, New York.

Going viral. Researchers are tweaking the capsid of adeno-associated viruses to optimize gene therapies for a multitude of disease. Shown here, AAV2.

From Zolgensma to Alzheimers? If the failure of the nerve growth factor therapy tempered enthusiasm for gene therapy (Mar 2018 news), then the success of AVXS-101, aka Zolgensma, reignited it. Developed by scientists at Nationwide Childrens Hospital, Columbus, Ohio, and AveXis, Bannockburn, Illinois, AVXS-101 uses an adeno-associated virus to deliver billions of copies of the survival motor neuron 1 gene to the brain. A small pilot trial tested the therapy in babies with spinal muscular atrophy (SMA) Type 1, the severest form of this neurodevelopmental disease. Lacking functional SMN1, these infants face progressive muscle weakness. Most die before their second birthday; those who live need a ventilator to breathe.

In Phase 1, AVXS-101 dramatically improved motor function of 15 treated infants; all were living 20 months later when historical data predicted only one would survive. Twelve babies who received the highest dose grew stronger within months, most sitting independently and rolling over. They hit the highest score on a scale of motor function, whereas untreated babies deteriorated. By 20 months, two of the treated babies had begun to walk (Mendell et al., 2017). The Food and Drug Administration approved zolgensma in May 2019. At SfN in Chicago, Petra Kaufmann, AveXis, played videos of the first patients treated with AVXS-101. Some four years later, they are walking, running, and appear to be playing almost normally. A video of a little girl walking downstairs with nary a hint of having SMA Type I visibly moved the audience.

Scientists say its a game-changer. It is really the tremendous success with SMA that has renewed interest in gene therapy, said Clive Svendsen, Cedars-Sinai Regenerative Medicine Institute, Los Angeles. Speaking with Alzforum before SfN, Bart De Strooper, Dementia Research Institute, London, said the same. The success in SMA patients of both gene therapy and antisense therapy has revived interest in the whole area, De Strooper said. Nowadays, researchers tend to lump gene therapy and antisense therapy under one moniker, i.e., gene-based therapy. The SMA antisense therapy nusinersen also works in babies with SMA Type 1 and is FDA-approved (Nov 2016 news; May 2018 conference news). Unlike gene therapy, antisense therapy needs to be delivered indefinitely.

How About Neurodegenerative Disease?At SfN, scientists outlined strategies for treating adults who face years of decline due to Alzheimers, amyotrophic lateral sclerosis, frontotemporal dementia, Huntingtons (HD) and Parkinsons diseases (PD), or other synucleinopathies. Some are being tested in clinical trials, others are in preclinical development. Some target specific losses or gains of function, others aim to rescue dying neurons more broadly. Scientists also believe that working on rare childhood diseases of lysosomal storage may give them an opening to treat this common phenotype in age-related neurodegeneration, as well.

Just this October, an ApoE gene therapy trial started enrolling. Led by Ronald Crystal at Weill Cornell Medical College, New York, it will inject adeno-associated virus carrying the gene for ApoE2 into patients with early to late-stage AD who inherited two copies of ApoE4. The idea is to flood their brains with the protective allele of this apolipoprotein to try to counteract the effects of the risk allele. AAV-rh10-APOE2 will be injected directly into the subarachnoid cisternae of participants brains. The Phase 1 trialwill recruit 15 patients with biomarker-confirmed AD. Beverly Davidson, Childrens Hospital of Philadelphia, has a similar ApoE2 gene therapy in preclinical development.

At SfN, Abeliovich detailed Prevails programs for forms of PD and for frontotemporal dementias that are caused by risk alleles. A trial has begun for a glucocerebrosidase-based gene therapy. The enzyme GCase is essential for lysosomes to function properly. People who have loss-of-function mutations in both copies of the GBA1 gene develop Gauchers, a lysosomal storage disease. The severest form starts in babies, most of whom die before age 2. Milder forms cause later-onset Gauchers, while heterozygous mutations in GBA1 increase risk for Parkinsons, making restoration of GCase an obvious strategy for PD. Some researchers are trying to develop ways to boost activity of the mutated enzyme (e.g., Oct 2019 news), whereas Abeliovich and colleagues have constructed AAV-9 vectors to deliver normal GBA1 into the brain to restore GCase production.

In preclinical studies, the AAV9-GBA1 construct PR001 rescued both lysosomal and brain function in models of GCase deficiency and of Parkinsons, Abeliovich said. In mice fed the GCase inhibitor conduritol epoxide (CBE), PR001 injected into the brain ventricles beefed up GCase activity and reduced glycolipid accumulation, which is a sign that lysosomes are functional. A single dose worked for at least six months. Similar results were seen in a commonly used model of Gauchers that expresses the V394L GBA mutation and only weakly expresses prosaposin and saposins, lysosomal proteins that metabolize lipids. In these 4L/PS-NA mice, PR001 made increased levels of active GCase, fewer lipids accumulated, and the mice were more mobile on a balance beam. 4L/PS-NA mice also accumulate -synuclein, the major component of Lewy bodies in PD and other synucleinopathies. In these mice, and also in A53T -synuclein mice made worse with CBE, PR001 halved the amount of insoluble -synuclein, Abeliovich reported at SfN.

In search of the right dose for humans, the scientists next turned to nonhuman primates. They injected PR001 into the cisterna magna in hopes AAV9 would broadly distribute throughout the brain. At the highest dose, 8 x 1010 capsids per gram of brain weight, exposure in the brain was similar to that seen in the mice. The virus permeated the spinal cord, frontal cortex, hippocampus, midbrain, and putamen.

Also in October, Prevail scientists began recruiting for a Phase 1/2 double-blind, sham-controlled trial to test this gene therapy in 16 people with moderate to severe PD, who have mutations in one or both copies of their GBA1 genes. Six patients each will receive a low or high dose of PR001A. Blood and CSF biomarkers to be analyzed at three and 12 months, and at follow-up, include GCase, lipids, -synuclein, and neurofilament light chain. Participants will also undergo cognitive, executive, and motor-function tests and brain imaging. A Phase 1/2 trial of PR001 in neuronopathic Gauchers, which affects the brain and spinal cord, will start soon, Abeliovich said.

Other groups are boosting dopamine production in Parkinsons by way of gene therapy. VY-AADC,developed by Voyager Therapeutics, Cambridge, Massachusetts, packages the gene for L-amino acid decarboxylase (AADC), which converts L-dopa into dopamine, in an AAV-2 vector that is delivered into the brain. Two Phase 1 open-label trials are testing safety and efficacy. Both the PD-1101 and PD-1102 trials use MRI to guide injections of the vector bilaterally into the putamina of 15 or 16 patients, respectively. According to preliminary results presented at the annual meeting of the American Academy of Neurology this past May, the virus penetrated half of the putamen and AADC activity, as judged by 18F-DOPA PET, increased by 85 percent in the latter study. Seven of eight treated patients reported improvement after a year, along with longer on time on L-DOPA, and shorter off time. Off time is the period when L-DOPA effects wear off and patients experience loss of motor control. RESTORE-1, a Phase 2 study of 42 patients, started in 2018 and will run to the end of 2020.

Long-Lived Gene Therapy. When a Parkinsons disease patient died eight years after neurturin gene therapy, the trophin was still being expressed in their putamen (top left) and substantia nigra (bottom left), where it corresponded with tyrosine hydroxylase activity (right). [Courtesy of Jeff Kordower.]

Also in PD, Kordower and colleagues plan to re-evaluate neurturin-based gene therapy. Previously, the gene for this neurotrophin was delivered in an AAV2 vector into the brains of Parkinson patients in Phase 1 and 2 trials. This did not improve motor function. Even so, in Chicago Kordower showed that in two patients who died eight and 10 years later, the inserted gene was still expressing neurturin and that dopamine levels were higher on the injected than the contralateral side of the substantia nigra/putamen. This shows us that long-term gene expression can be achieved in the human brain, said Kordower (see image above). He believes that by focusing delivery with ultrasound, or tweaking the capsid itself, he may be able to generate enough gene expression to improve function.

Separately, AAV-GAD, a gene therapy for PD that showed promise in Phase 2 (Mar 2011 news) was acquired by MeiraGTx, New York, which will continue to develop it in the U.S. and Europe, according to founder Samuel Waksal (Nov 2018 news).

For its part, Prevail has a gene transfer construct for frontotemporal dementia in the pipeline, as well. Called PR006, it carries GRN, the gene encoding progranulin, on an AAV9 vector. GRN mutations cause familial FTD and, much like GBA mutations, do their dirty work via lysosomal dysfunction. In Chicago, Abeliovich reported that PR006 boosted progranulin release from neurons derived from FTD-GRN patients, nearly doubling their levels of mature Cathepsin D, the lysosomal protease that chops progranulin into granulins and indicates healthy lysosomes. In progranulin knockout mice, PR006 restored brain GRN expression and progranulin secretion into the CSF. Abeliovich said he expects a Phase 1/2 clinical trial in FTD patients to start in early 2020.

The biotech company Passage Bio, Philadelphia, is planning for clinical trials early next year with its AAV-GRN vector. MeiraGTx, New York, is banking on a different approach for FTD. They have developed an AAV carrying UPF1, which encodes regulator of nonsense transcripts 1. This protein helps clear out aberrant RNAs through a process call nonsense-mediated decay. MeiraGTx hopes this will restore homeostasis to RNA processing. AAV-UPF1 will be trialed for FTD and all forms of ALS bar those caused by mutations in SOD1. For SOD ALS, Novartis, Basel, Switzerland, and REGENXBIO, Rockville, Maryland, have a vector in preclinical testing.

For his part, Svendsen is taking a different approach. His lab tackles ALS with ex vivo gene therapy. The idea is to engineer clinical-grade human stem cells to produce glial-derived growth factor, and inject them into the spinal cord, much like the early NGF studies did in AD. Svendsen hopes the cells will churn out enough of the neurotrophin to protect spinal cord motor neurons. In a Phase 1/2a trial, 18 ALS patients have received these cells into one side of their spinal cords, such that each person serves as his or her own control. If this works, they would regain mobility only on the injected side. The trial finished in October; Svendsen expects results to come out in a few months. In a follow-up study, the scientists are trying to do the same with induced pluripotent stem cells. This would allow them to transplant autologous cells into patients, avoiding immune rejection

Other groups are deploying gene therapy as a way to improve immunotherapy, shield neurons from stress, or even generate neurons from astrocytes to make up for those lost to neurodegeneration.Tom Fagan

Read more here:
Time to Try Again: Gene-Based Therapy for Neurodegeneration - Alzforum

I have a four-foot-tall robot in my house that plays with my kids. Its name is Jethro.

Both my daughters, aged 5 and 9, are so enamored with Jethro that they have each asked to marry it. For fun, my wife and I put on mock weddings. Despite the robot being mainly for entertainment, its very basic artificial intelligence can perform thousands of functions, including dance and teach karate, which my kids love.

The most important thing Jethro has taught my kids is that its totally normal to have a walking, talking machine around the house that you can hang out with whenever you want to.

Given my daughters semi-regular use of smartphones and tablets, I have to wonder how this will affect them in the future. Will they have any fear of technologies like driverless cars? Will they take it for granted that machine intelligences and avatars on computers can be their best friends, or even their bosses?

Will marrying a super-intelligent robot in 20 years be a natural decision? Even though I love technology, Im not sure how I would feel about having a robot-in-law. But my kids might think nothing of it.

This is my story of transhumanism.

Courtesy of Zoltan Istvan

My transhumanism journey began in 2003 when I was reporting a story for National Geographic in Vietnams demilitarized zone and I almost stepped on a landmine.

I remember my guide roughly shoving me aside and pointing to the metal object half sticking out of the ground in front of me.

I stared at the device that would have completely blown my legs off had my boot tripped the mine. I had just turned 30. The experience left me shaken. And it kept haunting me.

That night as I lay tense and awake in my hotel room, I had the epiphany that has helped define the rest of my life: I decided that the most important thing in my existence was to fight for survival. To put it another way: My goal was to never die.

Because I was not religious, I immediately turned to the thing that gave meaning to my world: science and technology. I took a leap of faith and made a wager that day. I later called this (and even later, dedicated a book to it) the transhumanist wager.

The life extension business of transhumanism will be a $600 billion industry by 2025.

My idea for an immortality wager came from Pascals Wager, the famous bet that caught on in the 17th century that loosely argued it was better to believe in God than not to, because you would be granted an afterlife if there was indeed a God. My transhumanist wager was based in my belief that its better to dedicate our resources to science and technology to overcome death while were still aliveso we dont ever have to find out whether there is an afterlife or not. It turns out I wasnt alone in my passion to live indefinitely through science. A small social movement, mostly of academics and researchers, were tackling similar issues, starting organizations, and funding research.

Some of them called themselves transhumanists.

Fast-forward 16 years from my landmine incident, and transhumanism has grown way beyond its main mission of just overcoming death with science.

Now the movement is the de facto philosophy (maybe even the religion) of Silicon Valley. It encapsulates numerous futurist fields: singularitarianism, cyborgism, cryonics, genetic editing, robotics, AI, biohacking, and others.

Biohacking in particular has taken offthe practice of physically hacking ones body with science, changing and augmenting our physiology the same way computer hackers would infiltrate a mainframe.

Its pretty obvious why it has emerged as such a big trend: It attracts the youth.

Not surprisingly, worrying about death is something that older people usually do (and, apparently, those younger people who almost step on landmines). Most young people feel invincible. But tell young people they can take brain drugs called nootropics that make them super smart, or give them special eye drops that let them see in the dark, or give them a chip implant that enhances human ability (like the one I have), and a lot of young people will go for it.

In 2016, I ran for the US presidency as the Transhumanist Party nominee. To get support from younger biohackers, my team and I journeyed on the Immortality Busmy 38-foot coffin-shaped campaign busto Grindfest, the major annual biohacking meet-up in Tehachapi, California. In an old dentists chair in a garage, biohackers injected me with a horse syringe containing a small radio-frequency-identification implant that uses near-field communication technologythe same wireless frequency used in most smartphones. The tiny deviceits about the size of a grain of ricewas placed just under the skin in my hand. With my chip, I could start a car, pay with bitcoin, and open my front door with a lock reader.

Four years later, I still have the implant and use it almost every day. For surfers or joggers like myself, for example, its great because I dont have to carry keys around.

One thing I do have to navigate is how some religious people view me once they understand I have one. Evangelical Christians have told me that an implant is the mark of the beast, as in from the Bibles Book of Revelations.

Even though Im tagged by conspiracy theorists as a potential contender for the Antichrist, I cant think of any negatives in my own experiences to having a chip implant. But as my work in transhumanism has reached from the US Military to the World Bank to many of the worlds most well-known universities, my chip implant only exasperates this conspiracy.

While people often want to know what other things Ive done to my body, in reality becoming a cyborg is a lot less futuristic and drastic than people think.

For me and for the thousands of people around the world who have implants, its all about functionality. An implant simply makes our lives easier and more efficient. Mine also sends out pre-written text messages when peoples phones come within a few feet of me, which is a fun party trick.

But frankly, a lot of the most transformative technology is still being developed, and if youre healthy like me, theres really not much benefit in doing a lot of biohacking today.

I take nootropics for better brain memory, but theres no conclusive research I know of that it actually works yet. Ive done some brainwave therapy, sometimes called direct neurofeedback, or biofeedback, but I didnt see any lasting changes. I fly drones for fun, and of course I also have Jethro, our family robot.

For the most part, members of the disabled community are the ones who are truly benefiting from transhumanist technologies today. If you have an arm shot off in a war, its cyborg science that gives you a robot arm controlled by your neural system that allows you to grab a beer, play the piano, or shake someones hand again.

But much more dramatic technology is soon to come. And the hope is that it will be availableand accessibleto everyone.

I asked to be added to a volunteer list for an experiment that will place implants in peoples brains that would allow us to communicate telepathically, using AI. (Biohacking trials like this are secretive because they are coming under more intense legal scrutiny.)Im also looking into getting a facial recognition security system for my home. I might even get a pet dog robot; these have become incredibly sophisticated, have fur softer than the real thing (that doesnt shed all over your couch or trigger allergies) and can even act as security systems.

Beyond that, people are using stem cells to grow new teeth, genetic editing to create designer babies, and exoskeleton technology that will likely allow a human to run on water in the near future.

Most people generally focus on one aspect of transhumanism, like just biohacking, or just AI, or just brainwave-tech devices. But I like to try it all, embrace it all, and support it all. Whatever new transhumanist direction technology takes, I try to take it all in and embrace the innovation.

This multi-faceted approach has worked well in helping me build a bridge connecting the various industries and factions of the transhumanist movement. Its what inspired me to launch presidential and California gubernatorial campaigns on a transhumanist platform. Now Im embarking on a new campaign in 2020 for US president as a Republican, hoping to get conservatives to become more open-minded about the future.

The amount of money flowing into transhumanist projects is growing into many billions of dollars. The life extension business of transhumanism will be a $600 billion industry by 2025, according to Bank of America. This is no time for transhumanism to break apart into many different divisions, and its no time to butt heads. We need to unite in our aim to truly change the human being forever.

Transhumanistsit doesnt matter what kind you arebelieve they can be more than just human. The word natural is not in our vocabulary. Theres only what transhumanists can do with the tools of science and technology they create. That is our great calling: to evolve the human being into something better than it is.

Because transhumanism has grown so broadly by now, not all transhumanists agree with me on substantially changing the human being. Some believe we should only use technology to eliminate suffering in our lives. Religious transhumanists believe we should use brain implants and virtual reality to improves our morality and religious behavior. Others tell me politics and transhumanism should never mix, and we must always keep science out of the hands of the government.

We need unity of some significant sort because as we grow at such a fast rate there are a lot of challenges ahead. For example, the conservative Christian Right wants to enact moratoriums against transhumanism. The anarcho-primativists, led by people like the primitivist philosopher and author John Zerzan (who I debated once at Stanford University), want to eliminate much technology and go back to a hunting-gathering lifestyle which they believe is more in tune with Earths original ecology. And finally, we must be careful that the so-called one percent doesnt take transhumanist technology and leave us all in the dust, by becoming gods themselves with radical tech and not sharing the benefits with humanity.

I personally believe the largest danger of the transhumanist era is the fact that within a few decades, we will have created super-intelligent AI. What if this new entity simply decides it doesnt like humans? If something is more sophisticated, powerful, intelligent, and resilient than humans, we will have a hard time stopping it if it wants to harm or eliminate us.

Whatever happens in the future, we must take greater care than we ever have before as our species enters the transhumanist age. For the first time, we are on the verge of transforming the physical structure of our bodies and our brains. And we are inventing machines that could end up being more intelligent and powerful than we are. This type of change requires that not only governments act together, but also cultures, religions, and humanity as a whole.

In the end, I believe that a lot more people will be on board with transhumanism than admit it. Nearly all of us want to eliminate disease, protect our families from death, and create a better path and purpose for science and technology.

But I also realize that this must be done ever so delicately, so as not to prematurely push our species into crisis with our unbridled arrogance. One day, we humans may look back and revel in how far our species has evolvedinto undying mammals, cyborgs, robots, and even pure living data. And the most important part will be to be able to look back and know we didnt destroy ourselves to get there.

Go here to read the rest:
What it means to be a cyborg in 2019 - Quartz

November is Alzheimers Awareness Month. Its a fitting time to look at the latest Israeli advances in preventing, diagnosing and treating the progressive and incurable brain disorder.

Alzheimers disease (AD) is the most common cause of the 9.9 million new cases of dementia diagnosed each year worldwide. The disease primarily strikes the elderly population, affecting 30 percent of those over age of 85.

AD impacts memory, thinking and language skills, and even the ability to carry out simple tasks.

The disease occurs when a protein called amyloid beta aggregates in brain tissues. These protein clumps kill nerve cells, leading to damage in the brain-function mechanisms.

Here are 10 examples of promising Israeli approaches reported within the past two years alone.

PREVENTION

Various genetic, lifestyle and environmental factors can put a person at risk for AD. Among them are diabetes, high blood pressure, obesity, smoking, depression, cognitive inactivity or low education, and physical inactivity.

Preventing the onset of AD is the focus of these approaches:

Eitan Okun, Alzheimers disease researcher at Bar-Ilan University. Photo: courtesy

Most vaccines work by mounting an immune response toward a weakened pathogen to boost the immune systems ability to fight the real pathogen.

Okuns approach primes the body to attack amyloid beta protein clumps in the brain, the signature sign of AD.

Following experiments on mice, Okun is preparing for human trials on people at known risk of developing the disease in their 50s or younger: those genetically inclined toward Alzheimers and people with Down syndrome.

These critical trials will determine whether the vaccine actually works in humans, said Okun. Depending on the success rate and side effects from [human] testing, we will be able to know how much more time is needed to make the vaccine available on a global scale.

Okun also is investigating new ways to diagnose AD earlier and more accurately using advanced MRI (magnetic resonance imaging) technologies to detect initial signs of amyloid protein aggregation in the brain.

BGU Prof. Alon Friedman has invented a new treatment to prevent neurological diseases. Photo courtesy of Dr. Merav Shamir

Introduced by BGN Technologies of Ben-Gurion University of the Negev, the novel therapy hinges on the fact that a malfunctioning BBB allows neurotoxic blood products to enter the brain and cause damage leading to neurological diseases.

The lab of Prof. Alon Friedman discovered that treating the BBB at early stages can protect the brain and prevent disease development.

Their proposed treatment would combine Memantine and Losartan, which have been shown in preclinical studies to protect the integrity of the BBB when administered together. Partners are being sought to continue development.

Prof. Ester Segal of the Technion. Photo: courtesy

They reported on this advance in a recent cover story of the journal Small.

Nanoscale silicon chips invented in Prof. Ester Segals lab allow for the direct insertion of neural growth factor protein into the brain and its gradual release into the target tissue, bypassing the BBB (see above). Afterward delivering all the therapeutic protein loaded onto them, the chips safely dissolve.

In a series of experiments, we showed in mice that the two ways of delivering the platform into the brain led to the desired result, said Technion doctoral student Michal Rosenberg.

Our technology has also been tested in a cellular model of Alzheimers disease and indeed, the protein release has led to rescuing the nerve cells.

DIAGNOSIS

PET scans and spinal taps are now the gold standard for diagnosing AD. Theyre both expensive and carry risks.

Cheaper, noninvasive tests being developed in Israel also could be critical in providing a much earlier diagnosis, when treatment would be most effective.

Thats because the same beta-amyloid proteins that clump in the brain of AD patients appear in the retina of the eyes up to 15 years before the onset of AD symptoms.

RetiSpec developed the retinal scanner at the Ontario Brain Institute in Canada. Clinical studies are ongoing in Israel and Canada.

In October, RetiSpec received the Alzheimers Drug Discovery Foundations Diagnostics Accelerator Award to fund continued development of its hyperspectral imaging technology.

This could allow doctors to compare brain scans taken over time from the same patient, and to differentiate between healthy and diseased brain tissue, without resorting to invasive or dangerous procedures such as brain tissue biopsies, explained lead researcher Dr. Aviv Mezer.

Clara is based on a relatively recent understanding that AD affects the brains orientation system before it affects memory.

The overlap between how the self is oriented to the world and the brain mechanisms that are disturbed by Alzheimers disease is astonishing, Arzy told ISRAEL21c.

Clara asks patients questions about themselves and their relationships to people, places and events. It then compares that information to a baseline and generates a computer-based test tailored for the individual that can diagnose very early Alzheimers.

The team from Dr. Shahar Arzys computational neuropsychiatry lab at Hadassah Hebrew University Medical Center in Jerusalem. Photo: courtesy

According to a study Arzys team published in the Proceedings of the National Academy of Sciences and in the American Psychological Associations journal Neuropsychology, Clara is 95 percent accurate.

Clara is now in the midst of a five-year test at Harvard to compare data generated by the system with data from AD markers taken via amyloid PET scan, quantitative and functional MRI and other neuropsychological tests.

Jaul and Oded Meiron (a cognitive neuroscientist who heads the Electrophysiology and Neuro-cognition Lab in Herzogs Clinical Research Center for Brain Sciences) published an articlein the Journal of Alzheimers Disease outlining their discovery of the link between the two conditions.

The reason is that the abnormal changes in the brain that lead to dementia are happening in other parts of the body, including the skin. Skin tissue and brain tissue derive from the same embryonic stem cells.

Jaul and Meiron are working with an American company to develop a test to identify a biomarker for abnormal cell density in the skin of dementia patients. They hope that this skin test could pinpoint an individuals type and stage of dementia. The biomarkers show the most promise in identifying AD, they say.

TREATMENT

A variety of approved medications for AD including Exelon, developed in Israel cannot cure or stop the progression of the disease. They only relieve or delay AD symptoms, such as memory loss and confusion.

A few Israeli pharmaceuticals under development aim to improve Alzheimer treatment options.

Breathing in pure oxygen in a pressurized room or chamber stimulates the release of growth factors and stem cells, which promote healing.

This revolutionary treatment for Alzheimers disease uses a hyperbaric oxygen chamber, which has been shown in the past to be extremely effective in treating wounds that were slow to heal, said lead researcher Prof. Uri Ashery.

Asherys group tested the therapy on a mouse model of Alzheimers disease. The treatment was found to reduce behavioral deficiencies compared to control mice.

Remarkably, the treatment also reduced plaque pathology and neuroinflammation in the test mice by about 40 percent.

Further research will investigate the underlying mechanisms of the therapy and evaluate its beneficial effects in Alzheimer patients.

Yotam Nisemblat, CEO of ProteKt Therapeutics. Photo: courtesy

Incubated at FutuRx in Ness Ziona, ProteKt was spun out of PKR kinase inhibitor research by University of Haifa Prof. Kobi Rosenblum. Inhibition of the enzyme PKR is a unique idea for improving memory consolidation.

Protein aggregation tends to increase with age and can lead to neurodegeneration because proteins can adopt an erroneous configuration, where theyre misfolded, explains Prof. Martin Kupiec.

The paper he and his colleagues published in Molecular Cell describes how removing glucose from a particular aggregated protein made the blob dissolve.

If the results can be replicated in more complex proteins, scientists will have a new research avenue toward treatments that could reverse the neurodegenerative effect of protein aggregates, Kupiec says.

Continue reading here:
10 promising developments that can help Alzheimer's patients - ISRAEL21c

Inflammatory bowel disease (IBD) is an umbrella term for two conditions, Crohns disease and ulcerative colitis, that are characterized by chronic inflammation of the gastrointestinal (GI) tract. This chronic and prolonged inflammation results in damage to the GI tract.

Historically IBD has been predominantly seen in industrialized countries, with the highest reported prevalence values in Europe and North America. In the United States alone, approximately 1.6 million people currently have Crohns disease or ulcerative colitis, and as many as 70,000 new cases of IBD are diagnosed each year. Although the incidence of IBD in North America and Europe is currently reported to be stabilizing or decreasing, the burden remains high as prevalence exceeds 03%. Over the last 30 years, the predominance of IBD has accelerated in newly industrialized countries including Africa, Asia and South America. Reports of IBD appear to be higher in urban areas than in rural areas, as well as in higher socio-economic classes. Individuals who immigrate to industrial urbanized developed nations before adolescence and those immigrants who initially belonged to a low-incidence population show a significantly higher incidence of IBD. This rise has been attributed to the rapid modernization and westernization of the population.

The reported rise in the number of people living with inflammatory bowel disease reflects a need for more research to find a cure. This article explores current therapies, drugs in the pipeline and disease outlook for patients and their caregivers living with IBD.

Overview

Inflammatory Bowel Disease is a broad term that describes conditions characterized by chronic inflammation of the gastrointestinal tract. The GI tract is responsible for the digestion of food, absorption of nutrients and elimination of waste. Inflammation impairs the ability of affected GI organs to function properly, leading to symptoms such as persistent diarrhea, abdominal pain, rectal bleeding, weight loss and fatigue. The two most common inflammatory bowel diseases are Crohns disease and ulcerative colitis.

Causes:

The exact cause of IBD is not entirely understood, however, it is known to involve an interaction between the immune system, genes and environmental factors.

In people with IBD, the immune system mounts an inappropriate response to the intestinal tract, resulting in inflammation. This abnormal immune system reaction occurs in people who have inherited genes that make them susceptible to IBD. Unidentified environmental factors serve as the trigger that initiates the harmful immune response in the intestines.

Studies have shown that 5 to 20% of affected individuals have a first-degree relative (parent, child or sibling) with one of the diseases. Numerous genes and genetic mutations connected to IBD have been identified including a mutation in the NOD2/CARD15 gene. Up to 20% of IBD patients in North America and Europe may have a mutation in the NOD2/CARD15 gene. While genetic testing is possible, it is not currently a part of the diagnostic process for IBD. Genetic testing can identify a potential risk for IBD in an individual but cannot predict whether IBD will develop.

The environmental factors that trigger IBD are not known, but several potential risk factors have been studied. These include smoking, use of antibiotics, use of Nonsteroidal anti-inflammatory drugs, diet and geographic location (more prevalent in industrialized countries).

Life expectancy: People with Inflammatory Bowel Disease have a relatively normal life expectancy compared to the general population. However, people with Crohns disease have a slightly higher overall mortality rate than the general healthy population. The increase in deaths is largely due to conditions such as cancer (particularly lung cancer), chronic obstructive pulmonary disease, gastrointestinal diseases, (excluding Crohns disease), and diseases of the genital and urinary tracts. In addition, patients with extensive inflammation in the colon due to ulcerative colitis are at higher risk than the general population for dying from gastrointestinal and lung diseases.

Annual Cost: There are both direct and indirect costs associated with IBD. Direct medical costs include expenses for hospitalizations, physician services, prescription drugs, over-the-counter drugs, skilled nursing care, diagnostic procedures and other healthcare services. Indirect costs are the value of lost earnings or productivity. Indirect costs also include the value of leisure time lost.

Direct Costs: The annual direct cost of Crohns disease is estimated to be from $8,265 per patient to $18,963 per patient and the annual direct cost of ulcerative colitis is estimated to be from $5,066 per patient to $15,020 per patient. Extrapolating from this data to the current prevalence estimates of IBD (780,000 cases of Crohns disease and 907,000 cases of ulcerative colitis), the total annual direct costs for all patients with IBD in the United States is estimated to be between $11 billion to $28 billion.

Indirect Costs: Based on a national health survey in 1999, nearly 32% of symptomatic IBD patients reported being out of the workforce in a one-year period, incurring an indirect cost of an estimated $5,228 per patient, bringing the total indirect cost of IBD in 1999 to $3.6 billion.

Diagnostic Strategies

One or more of the following tests or procedures may be used to help confirm a diagnosis of IBD.

Blood tests to check for anemia or infection from bacteria or viruses. A fecal occult blood test may also be used to test for hidden blood in the stool. Although a blood test cannot confirm the presence of IBD, it can help rule out conditions that cause similar symptoms.

Endoscopic procedures such as colonoscopy, upper endoscopy, sigmoidoscopy, and capsule endoscopyare also used to diagnose IBD. These procedures provide clear and detailed views of the gastrointestinal tract and can help to differentiate between Crohns disease and ulcerative colitis.

Imaging testssuch as X-rays, CT scans, and MRI scans are often used in conjunction with endoscopic procedures. Imaging data can reveal signs of IBD in the lining of the intestines, such as tears, bleeding, inflammation, or an obstruction.

Current Therapies

There is no cure for IBD. The goal of treatment is to reduce the inflammation that triggers the signs and symptoms, thus providing relief as well as long-term remission and reduced risks of complications. IBD treatment usually involves either drug therapy or surgery. Classes of medications used to treat IBD include anti-inflammatories, immunosuppressants, biologics and antibiotics.

Anti-inflammatory drugs are often the first step in the treatment of inflammatory bowel disease. Anti-inflammatories include corticosteroids and aminosalicylates (5-ASA), such as Allergans mesalamine (Asacol HD, Delzicol, others), Salix Pharmas Colazal (balsalazide) and Uceris (budesonide) and AstraZeneca's Entocort EC.

Immune system suppressor medications are used to stem the immune response that releases inflammation-inducing chemicals in the intestinal lining. Some examples of immunosuppressant drugs include azathioprine (Azasan, Imuran), mercaptopurine (Purinethol, Purixan), cyclosporine (Gengraf, Neoral, Sandimmune) and methotrexate (Otrexup, Rasuvo, Rheumatrex Dose Pack, Trexall, Xatmep).

Tumor necrosis factor (TNF)-alpha inhibitors, or biologics, are a group of medicines that suppress the body's natural response to tumor necrosis factor (TNF), a protein produced by white blood cells that is involved in early inflammatory events. Examples include AbbVie's Humira (adalimumab), Janssen's Simponi (golimumab), UCB's Cimzia and infliximab (Remicade, Inflectra). Other commonly used biologic therapies are Tysabri (natalizumab), Entyvio (vedolizumab) and Stelara (ustekinumab).

Antibiotics may be used in addition to other medications or when infection is a concern. Frequently prescribed antibiotics include ciprofloxacin (Cipro) and metronidazole (Flagyl).

Drug Pipeline

A variety of targeted therapies are currently being explored through clinical trials. In addition to TNF-alpha inhibitors, aminosalicylates and glucocorticosteroids, common targets and mechanisms include:

As of October 2019, there are 730 clinical trials (not yet recruiting/active/active, no longer recruiting) listed on clinicaltrials.gov. Of these trials, 268 are in the United States and the remainder are across global sites. When broken down by phase, there are 63 trials in phase I, phase II has 132 trials, 101 phase III trials and the remainder are in phase IV or are other types of studies, including behavioral modification or observational studies, those using dietary supplements and various devices.

The IBD market contains a mixture of big and smaller sized pharma and biotech companies. The market share is dominated by Janssen with 5 drugs in all phases (I-III) and Pfizerwith 5 drugs in phase I and II. The remaining companies include Roche in collaboration with Genentechwith three drugs in phases I-III and AbbVie with three drugs in phase II, II/III and III.

The following analysis of selected drugs in the pipeline will briefly discuss how each drug works and where it is in clinical trials. This information was up to date as of October 2019. Any text in italics represents failed or terminated trials.

Note: This section is not meant to be completely comprehensive and may unintentionally exclude some drugs in development or clinical trials, especially those trials outside of the United States.

Janssen has five drugs in development for IBD: golimumab, ustekinumab, JNJ-64304500 (JNJ-4500/ IPH-2301/NN-8555), JNJ-67864238, guselkumab monotherapy and guselkumab combined with golimumab.

Pfizer also has five drugs in development for both Crohns disease and ulcerative colitis.

This trial was suspended in July due to an interruption in the supply of the radiolabeled material.

A phase II trial is underway to determine if PF-06687234 is effective and safe as add-on therapy to infliximab in subjects with active ulcerative colitis who are not in remission.

Genentech/Roche has three treatments in development for IBD.

A phase I trial is evaluating etrolizumab in pediatric patients of 4 to <18 years of age with moderate to severe ulcerative colitis (UC) or with moderate to severe Crohn's disease (CD).

Genentechs Phase III Etro Studies program is also underway, assessing its safety and efficacy in both UC and Crohns. During this trial, etrolizumab will be compared to other currently the U.S. FDA-approved drugs, namelyRemicade (infliximab) and Humira (adalimumab), and to placebo. There are five planned trials for patients with UC, and two for thosewith CD, to be carried out in the U.S., as well as one non-U.S. based trial in UC patients. All these studies arecurrently recruiting participants.

AbbVie has three drugs in development for inflammatory bowel disease.

Phase I

Aevi Genomics has partnered with Kyowa Kirin for AEVI-002, a human monoclonal antibody that binds an inflammatory protein found in intestinal tissue called LIGHT. The trial is evaluating AEVI-002 for severe pediatric-onset Crohns disease. Initial data are expected in the second half of 2019.

Assembly Biosciences is conducting a phase IB clinical trial of its lead investigational live biotherapeutic product (LBP) candidate, ABI-M201, in patients with mildly to moderately active UC. ABI-M201 is comprised of a dened consortium of gut commensal bacterial strains, specically selected based on their functional attributes to target key aspects of disease biology. Assembly and Allergan have entered into a collaboration to jointly develop LBP compounds for Ulcerative colitis (UC), Crohns Disease and Irritable Bowel Syndromes. ABI-M201 is the first LBP candidate under this collaboration.

Enteromeis partnered with Takeda for the co-development and co-commercialization of EB8018 (TAK018), a first-in-class, non-systemic, orally administered small molecule. EB8018 is specifically designed to remain gut-restricted and to block bacteria expressing the bacterial virulence factor, FimH, a key inducer of the inflammatory cascade in the intestine, thereby decreasing intestinal inflammation in patients with Crohns disease. Preliminary data from a Phase Ib clinical trial of EB8018 for the treatment of Crohns disease is expected in 2019. Takeda is planning to commence a phase II trial in November of 2019.

Gossamer Bio is developing GB004, an oral HIF-1 stabilizer. Patient enrollment in a Phase Ib study of active mild-to-moderate ulcerative colitis (UC) began during the second quarter, and the Company expects topline results from the study in the first half of 2020.

Intralytix, Inc.'s EcoActive bacteriophage therapy targeting adhesive invasive E. coli (AIEC) in Crohn's disease patients has entered a Phase I/IIa clinical trial at the Icahn School of Medicine at the Mount Sinai Hospital in New York, NY. The presence of AIEC in the intestines is associated with worsening inflammation in this disease. The trial will measure the effect of oral phage administration on the AIEC (CFU/g) in stools of patients receiving phages versus patients receiving a placebo.

Nutrition Science Partners Limited, a 50/50 joint venture between Chi-Med and Nestl Health Science SA, is assessing HMPL004-6599, a proprietary botanical (Andrographis paniculate) with in vitro inhibitory activity against TNF-, IL-1 and NF-B. A pilot study of A. paniculata extract (HMPL-004) indicated similar efficacy to mesalamine for ulcerative colitis. HMPL004-6599 is an enriched/purified re-formulation of HMPL-004, an anti-inflammatory with anti-TNF properties. A phase 3 trial of the original formulation was evaluating its efficacy in ulcerative colitis. However, the trial was terminated in 2014 following an interim analysis showing the endpoint was unlikely to be reached.

OSE Immunotherapeutics has a pipeline of drugs aimed at immune-oncology and autoimmune diseases, one of which is OSE-127. OSE-127 is a monoclonal immunomodulatory antibody targeting the CD127 receptor, the alpha chain of the interleukin-7 receptor (IL-7R) that induces a powerful antagonist effect on effector T lymphocytes. The blockage of IL-7R prevents the migration of pathogenic T lymphocytes while preserving regulator T lymphocytes (1,2,3,4) which have a positive impact in autoimmune diseases. The first patients were dosed in a phase I trial in December of 2018.

Phase II

AbGenomicsis evaluating neihulizumab/AbGn-168H, a humanized therapeutic antibody with a unique mechanism of action, which preferentially induces apoptosis of late-stage activated T cells. This activated-T cell apoptosis-inducing antibody effectively eliminates chronic pathogenic T cells while fully maintaining host defense. A phase II trial is currently enrolling up to 40 patients with moderate to severe active ulcerative colitis and who have failed or are intolerant to anti-TNF and/or anti-integrin therapy.

Allergan's brazikumab is an anti-inflammatory with the potential to curb inflammation by blocking the proinflammatory molecule interleukin-23. In a double-blind, placebo-controlled study of 119 adults with moderate to severe CD who had failed treatment with tumor necrosis factor antagonists, 8 and 24 weeks of treatment were associated with clinical improvement. Higher baseline serum concentrations of IL22 were associated with a greater likelihood of response to treatment compared withplacebo.

Two trials are currently underway, and both are utilizing a personalized approach to evaluate the role of biomarkers, such as IL22, in predicting treatment response to brazikumab.

The phase II EXPEDITION trial is comparing brazikumab to placebo or Entyvio (vedolizumab) in approximately 375 patients with moderately to severely active ulcerative colitis.

The phase IIb/III INTREPID trial is currently enrolling up to 1,140 patients with moderate to severe Crohns disease to evaluate brazikumab versus placebo and versus an active comparator, Humira (adalimumab).

Boehringer Ingelheimis developing Spesolimab (BI 655130) is a monoclonal antibody that blocks the action of the interleukin-36 receptor (IL-36R), a signaling pathway within the immune system that may play a role in many inflammatory diseases. Proof of concept was demonstrated in a phase I study in patients with generalized pustular psoriasis, an IL36-mediated skin disease.

Four clinical trials are currently underway for both Crohns disease and ulcerative colitis.

Bridge Biotherapeutics is evaluating BBT-401, a GI-tract restricted small molecule inhibitor of Pellino-1. Pellino-1 is a ligase acting as a critical mediator for a variety of immune receptor signaling pathways, including Toll-like receptors, interleukin-1 receptor and T-cell receptors. BBT-401 was proved to be well-tolerated and safe in a phase I study in 80 healthy volunteers. In addition, the PK data demonstrated its key feature of no or minimal systemic exposure. A randomized, placebo-controlled, dose-escalation phase II trial is recruiting 48 patients with active ulcerative colitis.

Bristol-Myers Squibbs BMS-986165 is an oral, selective tyrosine kinase 2 (TYK2) inhibitor. TYK2, an intracellular signaling kinase, mediates cytokine-driven immune and pro-inflammatory signaling pathways that are critical in the cycle of chronic inflammation central to immune-mediated diseases. A phase II trial in patients with psoriasis was successfully completed in 2018. Two phase II trials are currently underway, one each in Crohns disease and ulcerative colitis.

Eli Lillyis progressing with mirikizumab (LY 3074828), a humanized IgG4 monoclonal antibody that binds and inhibits the p19 subunit of interleukin 23. Positive results have been reported from the phase II SERENITY trial in patients with Crohns disease and from a phase II trial for ulcerative colitis. Both trials showed that patients treated with mirikizumab achieved significantly greater rates of clinical and endoscopic remission at 12 weeks compared to placebo. Lilly is currently conducting six clinical trials in phase II and phase III, for both Crohns disease and ulcerative colitis.

Gilead, in global collaboration with Galapagos NV, is studying filgotinib, a highly selective JAK1 inhibitor. Results from a phase II study, FITZROY, were published in The Lancet in December of 2017. The study examined the efficacy and safety of filgotinib for the treatment of active moderate-to-severe Crohn's disease. Data showed filgotinib induced clinical remission in significantly more patients compared with placebo and had an acceptable safety profile. There are currently seven active phase II and III trials underway, including MANTA, DIVERSITY, DIVERGENCE2 and SELECTION 1.

Immunic Therapeutics is developing IMU-838, an oral tablet formulation of a small molecule drug (vidofludimus calcium), which inhibits dihydroorotate dehydrogenase (DHODH). Immunic completed two phase I studies in 2017, which evaluated single or repeated once-daily doses of IMU-838 in healthy volunteers. Results supported the tolerability of repeated daily dosing of up to 50 mg of IMU-838. A phase II trial, CALDOSE 1, is underway for ulcerative colitis.

Incyteis evaluating itacitinib, an orally administered small molecule Janus kinase 1 (JAK1) inhibitor. A double-blind, dose-ranging, placebo-controlled phase II trial is currently recruiting patients with moderate to severe ulcerative colitis.

Landos Biopharma's lead program is BT-11, an orally active, locally acting small molecule therapeutic that binds to LANCL2. In preclinical studies, it was shown to exert potent anti-inflammatory effects and was safe and well-tolerated with no dose-limiting toxicities in a phase I study. A phase II trial began in August of 2019 in patients with mild to moderate ulcerative colitis and is underway in Europe and the U.S. A second phase II study is anticipated to begin shortly in patients with moderate to severe Crohns disease, also in Europe and the United States.

Reistone Biopharma is developing SHR-0302, an orally administered selective JAK1 inhibitor. Two trials are underway: a phase II trial evaluating SHR0302 compared to placebo in patients with moderate to severe active ulcerative colitis and a phase II trial evaluating SHR-0302 in patients with moderate to severe active Crohn's Disease.

Seres Therapeutics is advancing with SER-287 is an oral capsule developed using Seres proprietary microbiome therapeutics platform. It is biologically-sourced and contains a consortium of live and diverse bacterial spores. SER-287 was designed to reduce the triggers of immune activation rather than suppress the immune system. Results from a phase Ib trial in patients with ulcerative colitis showed SER-287 microbiome treatment resulted in a dose-dependent benefit in clinical remission rates, and an improvement in endoscopic scores. A phase II trial, ECO-RESET, is currently recruiting 200 adults, age 18-80, with active mild-to-moderate ulcerative colitis.

Sublimity Therapeutics has developed an oral formulation of cyclosporine, referred to as ST-0529, using Sublimitys proprietary SmPill delivery system. Unlike conventional oral or intravenous cyclosporine, SmPill technology enables precise delivery of cyclosporine directly into diseased tissue in the colon, thus minimizing systemic exposure and unwanted side effects. In a phase IIa study ST-0529 was safe, well-tolerated and showed a numerically higher difference in remission rates in patients with mild-to-moderate ulcerative colitis compared to placebo after only four weeks of treatment. A phase IIb study, AURORA (CYC-202), is currently recruiting 280 subjects with moderately to severely active ulcerative colitis.

Theravanceand Janssen Biotech are collaborating on the development of TD-1473, an orally administered and intestinally restricted pan-Janus kinase (JAK) inhibitor. Data from a phase Ib trial demonstrated that four weeks of TD-1473 treatment produced signals of clinical, histologic, and biomarker activity in patients with moderately-to-severely active ulcerative colitis. A phase II trial, DIONE, is evaluating TD-1473 in subjects with moderately-to-severely active Crohn's Disease with up to 42 weeks of treatment. A phase II/III trial, RHEA, is evaluating the efficacy and safety of induction and maintenance therapy with TD-1473 in subjects with moderately-to-severely active ulcerative colitis with up to 60 weeks of treatment.

Phase III

Arena Pharmaceuticalsis developing etrasimod, a next-generation, once-daily, oral, highly selective sphingosine 1-phosphate (S1P) receptor modulator designed for optimized pharmacology and engagement of S1P receptor 1, 4 and 5, which may lead to an improved efficacy and safety profile. The phase II OASIS trial met primary and all secondary endpoints with statistical significance for patients with ulcerative colitis receiving 2 mg dose of etrasimod for 12 weeks. Based on these results, Arena initiated the global phase III ELEVATE UC program, which consists of two worldwide clinical trials and an open-label extension study. In addition, planning is underway for a phase II/III trial in patients with Crohns disease.

Celgene's ozanimod targets the sphingosine-1-phosphate (S1P)-1 and -5 receptors. Results from phase II trials were reported in October of 2017. In the phase II STEPSTONE open-label study, ozanimod demonstrated meaningful clinical and endoscopic improvements in patients with moderately to severely active Crohn's disease at week 12. In the phase II TOUCHSTONE open-label extension study, ozanimod continued to demonstrate clinically meaningful results in moderately to severely active ulcerative colitis across multiple measures of disease activity through week 92. Celgene currently has nine active studies underway for both forms of IBD.

EA Pharma, a joint venture between Eisai Groups gastrointestinal disease business and Ajinomoto Group, is evaluating AJM300 (carotegrast methyl) an orally-active small molecule that antagonizes the 4 integrin receptor. A phase III trial was initiated in June of 2018 to evaluate AJM300 in patients with active ulcerative colitis.

RedHill Biopharma is evaluating RHB-104, a formulation of the generic antibiotics clarithromycin, rifabutin and clofazimine that is designed to treat Crohns disease by wiping out Mycobacterium avium paratuberculosis (MAP) infection.Some studies have linked infection with the bacterium to Crohns disease. In July of 2018, positive results were reported from the MAP US study, which evaluated RHB-104 for Crohns disease. The primary endpoint was successfully achieved, with superior remission rate at week 26 in patients treated with RHB-104 versus placebo.

Shire, a Takedacompany, has moved into phase III development with ontamalimab (SHP 647), a fully human IgG2 monoclonal antibody that targets mucosal addressin cell adhesion molecule (MADCAM1). Shire licensed the drug from Pfizer in 2016. Results from a phase II trial in patients with ulcerative colitis were published in the journal The Lancet in 2017 and demonstrated the treatment was safe and well-tolerated in this patient population, and better than placebo for induction of remission. Seven phase III trials are currently recruiting patients with both ulcerative colitis and Crohns disease.

Preclinical Candidates

The following is a sampling of companies that are preparing to develop and investigate drugs and other therapeutics in the preclinical laboratory setting. Data gathered from these preclinical trials will be used to determine whether the drug/therapy will move forward with clinical testing in humans.

AntaraLife Science's lead human health product is referred to as GaRP (Gastrointestinal ReProgramming). The GaRP product is a microbiome-targeted multi-component dietary supplement that has been designed to address the primary underlying factors associated with IBD and IBS. It is being positioned as an adjunct to existing therapies and not to replace existing prescription medications. Antara has completed the preclinical program, which provided strong scientific evidence that GaRP can combat the underlying causes of chronic bowel conditions, including inflammation and dysbiosis of the microbiome. Antara anticipates submitting regulator applications to move into clinical trials by the end of 2019.

Prometheus Bioscienceshas partnered with Takeda to discover, develop, and commercialize targeted therapies for inflammatory bowel disease. The collaboration combines the proprietary bioinformatics discovery platform and companion diagnostic tools developed by Prometheus Biosciences with Takeda's expertise in gastroenterology and drug development, in order to discover and advance up to three targeted IBD therapeutics and companion diagnostics.

View post:
Inflammatory Bowel Disease Insight Report: Current Therapies, Drug Pipeline and Outlook - BioSpace

Gallant Stem Cell Therapy For Dogs is one of the product companies to be featured on Shark Tank Season 11 Episode 8. The story behind the birth of Gallant Stem Cell Therapy For Dogs is pretty interesting. Here are some of the unknown facts about Gallant and its founders, Aaron Hirschhorn.

Aaron Hirschhorn is the founder and former-CEO of the popular dog-sitting marketplace DogVacay. Aaron is a noted entrepreneur with more than 20 years of experience in building companies and investing in them. DogVacay app was launched in 2013 and Aaron managed to raise $47 million from his erstwhile investors.

Aaron was the finalist in the Ernst & Young Entrepreneur of the Year Award 2016. In April 2017, Aarons DogVacay app merged with Rover.com and eventually went on to become a $1 billion pet services marketplace.

Trouble struck Aarons life when he suffered a massive back injury and was forced to undergo stem cell treatment which yielded amazing results to his surprise. Aaron, being an ardent dog lover wondered why this cutting-edge medical technology of stem cell transplants cannot be applied to dogs.

As a result, Gallant was born in the middle of 2018. According to Gallant, Your pups stem cells haveincredible healing power. Extract and store these powerful cells during your pets spay/neuter, so that you can unleash their potential when your best friend needs it most.

Ever since its inception, the mission of Gallant stem cell therapy is to help pets live a healthier life and make use of the epic technology of stem cell therapy in saving the lives of tons of dogs.

Dogs enter their senior years around 7 and begin feeling the effects of aging as early as 4! Traditional methods of treatment for injury and age-related conditions are expensive and can have harmful side effects. Stem cells are incredible natural healers. However, up to 99% of stem cells are lost over time due to aging. This forms the bottomline of Gallants business problem.

Gallant raised $7 million investment in August 2019.

https://gallant.com/

From the moment you entrust Gallant with your dogs stem cells, were actively invested in their long-term health and well-being. Working in tandem with you and your veterinarian, we will collect and store these powerful cells now, so down the road we can help to treat the most common health problems your dog may face. We will also update you on new and potentially life-changing treatments as they become available.

Pick your pups stem cell storage plan you dont have to have a spay/neuter procedure scheduled yet! You can always add that in later. Our proprietary process requires no additional training, so any veterinarian you trust to alter your dog is qualified. Ahead of your dogs spay/neuter, we will connect with your vet and send our collection kit directly to their office.

2. Collect

On the big day, we align with your vet before the procedure and arrange for a courier. During your dogs spay/neuter procedure, your veterinarian will take out the stem cell-rich reproductive tissue they would normally discard into the collection kit.

3. Preserve

Once the tissue is received by our scientists, we send confirmation to both you and your veterinarian. Your dogs tissue is first inspected for quality before isolating the stem cells. The stem cells are then counted and frozen in liquid nitrogen to preserve their potency in our secure, state-of-the-art laboratory. Once this process is complete, you and your veterinarian will be notified that your pets stem cells are safely stored. The cells are then monitored by our team to ensure they stay perfectly preserved.

4. Treat

Your pets stem cells are at the ready to be sent to your veterinarian if/when treatment is needed. Treatments are out-patient procedures and cost about $300. A stem cell procedure is not painful to your pet and does not require anesthesia to administer.

Gallants stem cell therapy is receiving a lot of exciting reviews online. The therapy has been successful in saving scores of dogs with conditions like osteoarthritis, skin conditions, chronic dry eye.

Gallant is offering a $395 off discount for using the code SHARKTANK

How did Gallant fare in Shark Tank Season 11? What did the Sharks have to tell about it? Did Gallant Get a Deal on Shark Tank? More information to be updated soon in this post.

See the article here:
Shark Tank Season 11 Episode 8 Everything About Gallant Stem Cell Bank For Dogs As Seen on Shark Tank! Unknown Facts - TheNewsCrunch

While the rate of death from cancer has been declining since the 1990s, an estimated 9.6 million people died from cancer in 2018, making it the second-leading cause of death worldwide [1]. According to the NCI Cancer Trends Progress Report, in the United States, the incidence and death rates of some cancer types have also been increasing. Together, these facts indicate that despite tremendous recent progress, the research community unfortunately still has a long list of tasks to complete to end global suffering from cancer.

The clinical management of cancer has long been rooted in morphological and histopathological analyses for diagnosis, and the triad of surgery, chemotherapy, and radiation for treatment. However, we are quickly moving towards a pervasive reliance on high resolution, high throughput, molecular marker-based diagnostic as well as precision-targeted therapeutic modalities. The progressive development of the paradigm that defined molecular drivers of cancer has exposed therapeutic vulnerabilities; for example, the BCR-ABL1 gene fusion in chronic myeloid leukemia, KIT mutations in gastrointestinal stromal tumors, ERBB2 amplification in a subset of breast cancers, or EGFR mutations and ALK/ ROS/ RET gene fusions in lung cancers to name a few. Fueled by advances in high-throughput sequencing, it is increasingly practical (and arguably affordable) to systematically pursue Targeted Anticancer Therapies and Precision Medicine in Cancer.

PLOS ONE, together with PLOS Computational Biology, launched a Call for Papers earlier this year to increase understanding of this clinically important area. The scope of this call encompassed four areas: identification and classification of driver genes and somatic alterations; target and drug discovery; mechanisms of drug resistance; and early detection and screening.

Today, we are very happy to announce the launch of the resulting Collection. Featuring an initial set of nearly two dozen papers, with more to be added as they are published, these articles represent diverse facets of ongoing efforts in this area, where general knowledge of cancers serves to inform individual patients care, and at the same time particulars from individual cancer cases contribute to improved resolution of our general knowledge pool.

Somatic aberrations that are critical to the development, growth and progression of cancer are defined as drivers that are typically accompanied by large numbers of incidental aberrations referred to as passengers, acquired in the tumors due to the general chromosomal instability characteristic of advanced cancers. Distinguishing driver aberrations from passengers in individual tumors represents an active area of research that involves development of smarter analytical algorithms, as well as definitive functional characterization of candidate aberrations.

Emilie A. Chapeau et al. developed a conditional inducible transgenic JAK2V617F mouse model that recapitulates aspects of human myeloproliferative neoplasms, including splenomegaly, erythroid expansion and hyperproliferation of bone marrow, with some intriguing differences seen between male and female mice. Importantly, the disease phenotype was reversible when transgene expression was switched off. This work underscores the key role for JAK2V617F in the initiation and maintenance of myeloproliferative neoplasms, and suggests that inhibitors specific to this JAK2 mutation might be efficacious in this disease [2].

Using targeted exon sequencing and array comparative genomic hybridization (CGH), Gayle Pageau Pouliot et al. identified monoallelic mutations in Fanconi-BRCA pathway genes in samples collected from children with T cell acute lymphoblastic leukemia (T-ALL). These mutations appeared to arise in early stages of tumorigenesis, suggesting a potential role for Fanconi-BRCA pathway insufficiency in the initiation of T-ALL. Although PARP inhibitors did not affect viability of isolated T-ALL cells with monoallelic Fanconi-BRCA mutations, these cells were hypersensitive to UV irradiation in vitro or ATR inhibition in vivo, suggesting that ATR inhibitors might have therapeutic value in T-ALL [3].

Three papers in this Collection examine links between genetic alterations and prognosis. Sumadi Lukman Anwar et al. report that LINE-1 hypomethylation in human hepatocellular carcinoma samples correlates with malignant transformation, decreased overall survival and increased tumor size [4]. Investigating HER2-positive breast cancer specimens, Arsalan Amirfallah et al. found that high levels of vacuole membrane protein 1 (VMP1) could potentially contribute to cancer progression and might be a marker of poor prognosis [5]. Finally, in their systematic review and meta-analysis, Chia Ching Lee et al. identified low discordance rates in EGFR mutations between primary lung tumors and distant metastases, although they note some differences depending on metastatic site. Notably, discordance rates appear to be higher in bone metastases compared to central nervous system or lung metastases [6]. These studies provide much-needed leads for the potential development of new diagnostic tests or targeted therapies.

Precision therapy of cancers is premised on the identification of tumor-specific driver aberrations that are necessary for tumor growth and survival. These aberrations represent potential therapeutic targets. While matching therapeutics have been developed for some of the tumor-specific targets, particularly many oncogenic kinases, a large number of defined driver aberrations remain in search of effective therapies. Drug discovery efforts to match defined targets represent a vigorous area of ongoing research with implications for survival and quality of lives of cancer patients worldwide. The development of drugs to treat cancers driven by transcription factors, chromatin modifiers, and epigenetic modulators has proved particularly challenging. On the other hand, recent development of novel immunotherapeutic approaches has spurred research to identify potential targets and matching drug discovery efforts.

This Collection highlights several interesting new strategies to identify potential lead compounds for cancer treatment. Thomas W. Miller et al. describe the development of a biochemical quantitative high-throughput screen for small molecules that disrupt the interaction between CD47 and SIRP. Preclinical studies have shown that disrupting this interaction may provide a new approach for cancer immunotherapy. Small molecular inhibitors that specifically target the interaction between CD47 and SIRP are potentially advantageous over biologics that target CD47, because they might have less on target toxicologic issues and greater tissue penetrance [7].

Work from Gabrielle Choonoo, Aurora S. Blucher et al. examines the feasibility of repurposing existing cancer drugs for new indications. The authors compiled information about somatic mutations and copy-number alterations in over 500 cases of head and neck squamous cell carcinoma (HNSCC) and mapped these data to potential drugs listed in the Cancer Targetome [8]. This approach uncovered pathways that are routinely dysregulated in HNSCC and for which potential anti-cancer therapies are already available, as well as those for which no therapies exist. The work opens new therapeutic avenues in the treatment of this disease and also illuminates which pathways could be prioritized for the development of therapies [9].

Another important approach in extending the clinical utility of existing anti-cancer drugs is to determine whether they are effective in other settings. Indeed, Kirti Kandhwal Chahal et al. have demonstrated that the multi-tyrosine kinase inhibitor nilotinib, which is approved for use in chronic myeloid leukemia, binds the Smoothened receptor and inhibits Hedgehog pathway signaling. Nilotinib decreased viability of hedgehog-dependent medulloblastoma cell lines in vitro and in patient-derived xenografts in vivo, suggesting that nilotinib might be an effective therapy in Hedgehog-dependent cancer [10]. (Check out the authors preprint of this article on bioRxiv.) Darcy Welch, Elliot Kahen et al. took a different approach to identify new tricks for old drugs. By testing two-drug combinations of five established (doxorubicin, cyclophosphamide, vincristine, etoposide, irinotecan) and two experimental chemotherapeutics (the lysine-specific demethylase 1 (LSD1) inhibitor SP2509 and the HDAC inhibitor romidepsin), they found that combining SP2509 with topoisomerase inhibitors or romidepsin synergistically decreased the viability of Ewing sarcoma cell lines in vitro [11].

Two papers in this collection describe potential new therapeutic approaches in cancer. Vagisha Ravi et al. developed a liposome-based delivery mechanism for a small interfering RNA targeting ferritin heavy chain 1 (FTH1) and showed that this increased radiosensitivity and decreased viability in a subpopulation of glioma initiating cells (GICs) [12]. Yongli Li et al. identified 2-pyridinealdehyde hydrazone dithiocarbamate S-propionate podophyllotoxin ester, a podophyllotoxin derivative that inhibits matrix metalloproteinases and Topoisomerase II. Treatment with this compound decreased the migration and invasion of human liver cancer cell lines in vitro, as well as growth of HepG2-derived tumors in mouse xenografts [13].

The success of precision cancer therapy targeting defined somatic aberrations is hampered by an almost inevitable, eventual treatment failure due to the emergence of drug resistance. Resistance often involves new mutations in the therapeutic target itself, or it may result due to activation of alternative pathways. Identification and therapeutic targeting of drug resistant clones represents an ongoing research problem with important practical implications for the clinical management of cancer.

Afatinib is a pan-human epidermal growth factor receptor (HER) inhibitor under investigation as a potential therapeutic option for people with gastric cancer; however, preclinical studies have found that some gastric cancer cell lines are resistant to afatinib treatment. Karolin Ebert et al. identify a potential mechanism behind this lack of response, demonstrating that siRNA-mediated knockdown of the receptor tyrosine kinase MET increases afatinib sensitivity of a gastric cancer cell line containing a MET amplification. As upregulation of MET has been linked to resistance to anti-HER therapies in other cancers, these findings support a role for MET in afatinib resistance in gastric cancer and suggest that combined afatinib and anti-MET therapy might be clinically beneficial for gastric cancer patients [14].

Identifying mechanisms to circumvent drug resistance is critically important to improve response and extend survival, but it is equally important to identify individuals who could be at risk of not responding to anti-cancer therapeutics. Lucas Maahs, Bertha E. Sanchez et al. report progress towards this end, showing that high expression of class III -tubulin in metastatic castration-resistant prostate cancer (CRPC) correlated with decreased overall survival and worse response rate (as measured by changes in prostate-specific antigen (PSA) levels) in CRPC patients who received docetaxel therapy. The development of a biomarker indicating potential treatment resistance to docetaxel could help develop treatment plans with the best chance of success [15].

The converse approach identifying biomarkers that correlate with drug sensitivity could help distinguish subsets of patients who would benefit most from a certain anti-cancer therapy. Kevin Shee et al. mined publicly available datasets to identify genes whose expression correlate with sensitivity and response to chemotherapeutics and found that expression of Schlafen Family Member 11 (SLFN11) correlates with better response to a variety of DNA-damaging chemotherapeutics in several types of solid tumors [16]. Separately, Jason C. Poole et al. validated the use of the Target Selector ctDNA assay, a technology developed by their group that allows the specific amplification of very low frequency mutant alleles in circulating tumor DNA (ctDNA). Testing for EGFR, BRAF and KRAS mutations yielded a very high, >99% analytical sensitivity and specificity with the capability of single mutant copy detection, indicating that accurate molecular disease management over time is possible with this minimally invasive method [17].

Work from Georgios Kaissis, Sebastian Ziegelmayer, Fabian Lohfe et al. uses a machine learning algorithm to differentiate subtypes of pancreatic ductal adenocarcinoma based on 1,606 different radiomic features. Intriguingly, the subtypes identified in their analysis correlated with response to chemotherapeutic regimens and overall survival [18]. An imaging approach taken by Seo Young Kang et al. demonstrates the potential power of fluorodeoxyglucose (FDG) PET/CT scans in determining the response of people with metastatic differentiated thyroid cancer to radioactive iodine treatment [19].

Since cancer growth and development accrues progressive accumulation of somatic aberrations, early detection holds the promise of more effective interventions. Similarly, screening of at risk demographics has been found effective in preventing or better managing cancer care, as exemplified by the significant reduction in cases of cervical cancer after the introduction of the Pap smear as well as human papillomavirus (HPV) testing.

Biomarker development is also critically important for the early detection of cancer and metastatic disease; moreover, biomarkers are being identified that can provide insight into patient prognosis. Several papers in this Collection report interesting findings in the area of biomarker development. A report from Lingyun Xu et al. describes a magneto-nanosensor-based multiplex assay that measures circulating levels of PSA and four proteins associated with prostate cancer. This approach segregates people with prostate cancer from those with benign prostate hyperplasia with high sensitivity and specificity [20].

Two articles provide new insight into markers of disease progression and survival. Vidya Balagopal et al. report the development of a 22-gene hybrid-capture next generation sequencing panel to identify measurable residual disease in patients with acute myeloid leukemia (AML). In their retrospective study, the panel was effective at detecting evidence for residual disease. Importantly, it correctly identified patients who had never relapsed in that no evidence of residual disease was detected in any of these respective samples. Once validated, this approach could potentially be useful in monitoring patients with AML to ensure that recurrence or relapse is identified as soon as possible [21]. Separately, Yoon-Sim Yap et al. use a label-free microfluidic platform to capture circulating tumor cells (CTCs) from people with breast cancer and show that absolute numbers of CTCs predict progression-free survival with higher levels of CTCs correlating with a worse prognosis [22].

Finally, Lucia Suzuki et al. report findings into a potential role for the intestinal stem cell marker olfactomedin 4 (OLFM4) as a biomarker for metastasis in esophageal adenocarcinoma. The authors found that OLFM4 expression was not significantly associated with disease-free or overall survival; however, low OLFM4 expression was detected in poorly differentiated early and advanced-stage esophageal adenocarcinoma and was an independent prognostic variable for lymph node metastasis [23].

This collection of studies encompassing the range of research topics under the banner of targeted anticancer therapies highlights the diversity, complexity and inter-disciplinary nature of research efforts actively contributing to our collective knowledge base with the hope to positively impact the lives of all cancer patients.

We would like to thank all Academic Editors and reviewers for their expert evaluation of the articles in this Collection as well as the authors for their contributions to this field. Special thanks to Senior Editor, Team Manager Emily Chenette for her invaluable help and guidance in publishing this Collection.

Andrew Cherniack

Andrew Cherniack is a group leader in the Cancer Program at the Broad Institute of MIT and Harvard and in the Department of Medical Oncology at the Dana Farber Cancer Institute. He led the Broad Institutes effort to analyze somatic DNA copy number alterations for The Cancer Genome Atlas (TCGA) and is now co-principal investigator of the Broad Institutes copy number Genome Data Analysis Center for the National Cancer Institutes Genomic Data Analysis Network (GDAN). He also leads the oncoming effort to identify new cancer therapeutic targets for the partnership with Bayer. Prior to joining the Broad Institute in 2010, Dr. Cherniack worked in both academia and industry, with a 9-year tenure at the Abbott Bioresearch Center following a similar time period in the Program in Molecular Medicine at UMass Medical School, where he was a postdoctoral researcher and a research assistant professor. Dr. Cherniack holds a Ph.D. in molecular genetics from Ohio State University and a B.A. in biology from the University of Pennsylvania.

Anette Duensing

Anette Duensing is an Assistant Professor of Pathology at the University of Pittsburgh School of Medicine and a Member of the Cancer Therapeutics Program at the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center. Dr. Duensings research focuses on bone and soft tissue sarcomas with the goal of identifying novel therapeutic approaches that target the underlying molecular biology of these malignancies. Her special interest and expertise are in gastrointestinal stromal tumors (GISTs), a sarcoma characterized by mutations in the KIT or PDGFRA receptor tyrosine kinases and the first solid tumor entity that was successfully treated with small molecule kinase inhibitors. Dr. Duensing holds an M.D. degree from the University of Hannover School of Medicine, Germany, and was a research scholar of the Dr. Mildred Scheel Stiftung fr Krebsforschung (German Cancer Aid/Deutsche Krebshilfe) at Brigham and Womens Hospital, Harvard Medical School. She is the recipient of an AACR Scholar-in-Training Award (AACR-AstraZeneca), a Young Investigator Award from The Liddy Shriver Sarcoma Initiative, a UPCI Junior Scholar Award, a Jeroen Pit Science Award, a Research Award from the GIST Group Switzerland and was named Hillman Fellow for Innovative Cancer Research. Dr. Duensing is co-founder and leader of the Pittsburgh Sarcoma Research Collaborative (PSaRC), a highly translational, interdisciplinary sarcoma research program. She is also affiliated with the Department of Urology at the University of Heidelberg, Germany. Dr. Duensing is an Academic Editor for PLOS ONE and author of nearly 70 original articles, reviews and book chapters.

Steven G. Gray

Steven Gray graduated from Trinity College Dublin in 1992. He joined the laboratory of Tomas J. Ekstrm at the Karolinska Institute (Sweden) in 1996 and received his PhD in 2000. He moved to the Van Andel Research Institute in Michigan, USA where he continued his studies on the therapeutic potential of histone deacetylase inhibitors in the treatment of cancer. He also spent time as a visiting fellow at Harvard Medical School, Boston working on epigenetic therapies for neurodegenerative disease. Returning to Europe, Dr. Gray spent some time at the German Cancer Research Centre (DKFZ Heidelberg), and subsequently moved to Copenhagen to work for Novo Nordisk as part of the research team of Prof Pierre De Meyts at the Hagedorn Research Institute working on epigenetic mechanisms underpinning diabetes pathogenesis. Dr. Gray is currently a senior clinical scientist at St Jamess Hospital at the Thoracic Oncology Research Group at St. Jamess Hospital. He holds adjunct positions at both Trinity College Dublin (senior clinical lecturer with the Dept. of Clinical Medicine), and at Technical University Dublin (adjunct senior lecturer, School of Biology DIT). Dr. Gray has published over 100 peer-reviewed articles, 15 book chapters and has edited 1 book. Research in Dr Grays laboratory focuses on Receptor Tyrosine Kinases as potential therapeutic targets for the treatment of mesothelioma; epigenetic mechanisms underpinning drug resistance in lung cancer; targeting epigenetic readers, writers and erasers for the treatment of mesothelioma and thoracic malignancy; circulating tumour cells; and non-coding RNA repertoires in mesothelioma and thoracic malignancy.

Sunil Krishnan

Sunil Krishnan is the Director of the Center for Radiation Oncology Research and the John E. and Dorothy J. Harris Professor of Gastrointestinal Cancer in the department of Radiation Oncology at MD Anderson Cancer Center. He received his medical degree from Christian Medical College, Vellore, India and completed a radiation oncology residency at Mayo Clinic, Rochester, Minnesota. In the clinic, he treats patients with hepatobiliary, pancreatic and rectal tumors with radiation therapy. His laboratory has developed new strategies and tools to define the roles and mechanisms of radiation sensitization with gold nanoparticles, chemotherapeutics, biologics and botanicals. Dr. Krishnan serves as the co-chair of the gastrointestinal scientific program committee of ASTRO, co-chair of the gastrointestinal translational research program of RTOG, consultant to the IAEA for rectal and liver cancers, chair of the NCI pancreatic cancer radiotherapy working group, and Fellow of the American College of Physicians. He has co-authored over 200 peer-reviewed scientific publications, co-authored 17 book chapters, and co-edited 3 books.

Chandan Kumar-Sinha

Chandan Kumar-Sinha is a Research Associate Scientist in the Department of Pathology at the University of Michigan. He obtained Masters in Biotechnology from Madurai Kamraj University, and PhD in Plant Molecular Biology from Indian Institute of Science. He completed a Postdoctoral Fellowship at the Department of Pathology, University of Michigan, where he worked on genomic profiling of cancers. Thereafter, he joined the Advanced Center for Treatment, Research and Education in Cancer in India as a faculty member. After establishing a cancer genomics group there, he moved back to the University of Michigan to pursue translational cancer research. Dr. Kumar-Sinhas current research involves integrative clinical sequencing using high-throughput genome and transcriptome analyses to inform precision oncology. He has authored over 50 peer-reviewed publications, two book chapters, and is named co-inventor on a patent on prostate cancer biomarkers.

Gayle E. Woloschak

Gayle Woloschak is Professor of Radiation Oncology, Radiology, and Cell and Molecular Biology in the Feinberg School of Medicine, Northwestern University. Dr. Woloschak received her Ph.D. in Medical Sciences from the University of Toledo (Medical College of Ohio). She did her postdoctoral training at the Mayo Clinic, and then moved to Argonne National Laboratory until 2001. Her scientific interests are predominantly in the areas of molecular biology, radiation biology, and nanotechnology studies, and she has authored over 200 papers. She is a member of the National Council on Radiation Protection, the International Commission on Radiation Protection and numerous other committees and also serves on the US delegation to the United National Scientific Committee on the Effects of Atomic Radiation.

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Introducing the Targeted Anticancer Therapies and Precision Medicine in Cancer Collection - PLoS Blogs