jCyte starts second phase of stem cell clinical trial targeting vision loss

retinitis pigmentosas_1

How retinitis pigmentosa destroys vision

Studies show that Americans fear losing their vision more than any other sense, such as hearing or speech, and almost as much as they fear cancer, Alzheimer’s and HIV/AIDS. That’s not too surprising. Our eyes are our connection to the world around us. Sever that connection, and the world is a very different place.

For people with retinitis pigmentosa (RP), the leading cause of inherited blindness in the world, that connection is slowly destroyed over many years. The disease eats away at the cells in the eye that sense light, so the world of people with RP steadily becomes darker and darker, until the light goes out completely. It often strikes people in their teens, and many are blind by the time they are 40.

There are no treatments. No cures. At least not yet. But now there is a glimmer of hope as a new clinical trial using stem cells – and funded by CIRM – gets underway.

klassenWe have talked about this project before. It’s run by UC Irvine’s Dr. Henry Klassen and his team at jCyte. In the first phase of their clinical trial they tested their treatment on a small group of patients with RP, to try and ensure that their approach was safe. It was. But it was a lot more than that. For people like Rosie Barrero, the treatment seems to have helped restore some of their vision. You can hear Rosie talk about that in our recent video.

Now the same treatment that helped Rosie, is going to be tested in a much larger group of people, as jCyte starts recruiting 70 patients for this new study.

In a news release announcing the start of the Phase 2 trial, Henry Klassen said this was an exciting moment:

“We are encouraged by the therapy’s excellent safety track record in early trials and hope to build on those results. Right now, there are no effective treatments for retinitis pigmentosa. People must find ways to adapt to their vision loss. With CIRM’s support, we hope to change that.”

The treatment involves using retinal progenitor cells, the kind destroyed by the disease. These are injected into the back of the eye where they release factors which the researchers hope will help rescue some of the diseased cells and regenerate some replacement ones.

Paul Bresge, CEO of jCyte, says one of the lovely things about this approach, is its simplicity:

“Because no surgery is required, the therapy can be easily administered. The entire procedure takes minutes.”

Not everyone will get the retinal progenitor cells, at least not to begin with. One group of patients will get an injection of the cells into their worst-sighted eye. The other group will get a sham injection with no cells. This will allow researchers to compare the two groups and determine if any improvements in vision are due to the treatment or a placebo effect.

The good news is that after one year of follow-up, the group that got the sham injection will also be able to get an injection of the real cells, so that if the therapy is effective they too may be able to benefit from it.

Rosie BarreroWhen we talked to Rosie Barrero about the impact the treatment had on her, she said it was like watching the world slowly come into focus after years of not being able to see anything.

“My dream was to see my kids. I always saw them with my heart, but now I can see them with my eyes. Seeing their faces, it’s truly a miracle.”

We are hoping this Phase 2 clinical trial gives others a chance to experience similar miracles.


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CIRM Alpha Clinics Network charts a new course for delivering stem cell treatments

Sometimes it feels like finding a cure is the easy part; getting it past all the hurdles it must overcome to be able to reach patients is just as big a challenge. Fortunately, a lot of rather brilliant minds are hard at work to find the most effective ways of doing just that.

Last week, at the grandly titled Second Annual Symposium of the CIRM Alpha Stem Cell Clinics Network, some of those minds gathered to talk about the issues around bringing stem cell therapies to the people who need them, the patients.

The goal of the Alpha Clinics Network is to accelerate the development and delivery of stem cell treatments to patients. In doing that one of the big issues that has to be addressed is cost; how much do you charge for a treatment that can change someone’s life, even save their life? For example, medications that can cure Hepatitis C cost more than $80,000. So how much would a treatment cost that can cure a disease like Severe Combined Immunodeficiency (SCID)? CIRM-funded researchers have come up with a cure for SCID, but this is a rare disease that affects between 40 – 100 newborns every year, so the huge cost of developing this would fall on a small number of patients.

The same approach that is curing SCID could also lead to a cure for sickle cell disease, something that affects around 100,000 people in the US, most of them African Americans. Because we are adding more people to the pool that can be treated by a therapy does that mean the cost of the treatment should go down, or will it stay the same to increase profits?

Jennifer Malin, United Healthcare

Jennifer Malin from United Healthcare did a terrific job of walking us through the questions that have to be answered when trying to decide how much to charge for a drug. She also explored the thorny issue of who should pay; patients, insurance companies, the state? As she pointed out, it’s no use having a cure if it’s priced so high that no one can afford it.

Joseph Alvarnas, the Director of Value-based Analytics at City of Hope – where the conference was held – said that in every decision we make about stem cell therapies we “must be mindful of economic reality and inequality” to ensure that these treatments are available to all, and not just the rich.

“Remember, the decisions we make now will influence not just the lives of those with us today but also the lives of all those to come.”

Of course long before you even have to face the question of who will pay for it, you must have a treatment to pay for. Getting a therapy through the regulatory process is challenging at the best of times. Add to that the fact that many researchers have little experience navigating those tricky waters and you can understand why it takes more than eight years on average for a cell therapy to go from a good idea to a clinical trial (in contrast it takes just 3.2 years for a more traditional medication to get into a clinical trial).

Sunil Kadim, QuintilesIMS

Sunil Kadam from QuintilesIMS talked about the skills and expertise needed to navigate the regulatory pathway. QuintilesIMS partners with CIRM to run the Stem Cell Center, which helps researchers apply for and then run a clinical trial, providing the guidance that is essential to keeping even the most promising research on track.

But, as always, at the heart of every conference, are the patients and patient advocates. They provided the inspiration and a powerful reminder of why we all do what we do; to help find treatments and cures for patients in need.

The Alpha Clinic Network is only a few years old but is already running 35 different clinical trials involving hundreds of patients. The goal of the conference was to discuss lessons learned and share best practices so that number of trials and patients can continue to increase.

The CIRM Board is also doing its part to pick up the pace, approving funding for up to two more Alpha Clinic sites.  The deadline to apply to be one of our new Alpha Clinics sites is May 15th, and you can learn more about how to apply on our funding page.

Since joining CIRM I have been to many conferences but this was, in my opinion, the best one I have ever intended. It brought together people from every part of the field to give the most complete vision for where we are, and where we are headed. The talks were engaging, and inspiring.

Kristin Macdonald was left legally blind by retinitis pigmentosa, a rare vision-destroying disease. A few years ago she became the first person to be treated with a CIRM-funded therapy aimed to restoring some vision. She says it is helping, that for years she lived in a world of darkness and, while she still can’t see clearly, now she can see light. She says coming out of the darkness and into the light has changed her world.

Kristin Macdonald

In the years to come the Alpha Clinics Network hopes to be able to do the same, and much more, for many more people in need.

To read more about the Alpha Clinics Meeting, check out our Twitter Moments.

Stem Cell Stories that Caught our Eye: stem cell insights into anorexia, Zika infection and bubble baby disease

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Stem cell model identifies new culprit for anorexia.

Eating disorders like anorexia nervosa are often thought to be caused by psychological disturbances or societal pressure. However, research into the genes of anorexia patients suggests that what’s written in your DNA can be associated with an increased vulnerability to having this disorder. But identifying individual genes at fault for a disease this complex has remained mostly out of scientists’ reach, until now.

A CIRM-funded team from the UC San Diego (UCSD) School of Medicine reported this week that they’ve developed a stem cell-based model of anorexia and used it to identify a gene called TACR1, which they believe is associated with an increased likelihood of getting anorexia.

They took skin samples from female patients with anorexia and reprogrammed them into induced pluripotent stem cells (iPSCs). These stem cells contained the genetic information potentially responsible for causing their anorexia. The team matured these iPSCs into brain cells, called neurons, in a dish, and then studied what genes got activated. When they looked at the genes activated by anorexia neurons, they found that TACR1, a gene associated with psychiatric disorders, was switched on higher in anorexia neurons than in healthy neurons. These findings suggest that the TACR1 gene could be an identifier for this disease and a potential target for developing new treatments.

In a UCSD press release, Professor and author on the study, Alysson Muotri, said that they will follow up on their findings by studying stem cell lines derived from a larger group of patients.

Alysson Muotri UC San Diego

“But more to the point, this work helps make that possible. It’s a novel technological advance in the field of eating disorders, which impacts millions of people. These findings transform our ability to study how genetic variations alter brain molecular pathways and cellular networks to change risk of anorexia nervosa — and perhaps our ability to create new therapies.”

Anorexia is a disease that affects 1% of the global population and although therapy can be an effective treatment for some, many do not make a full recovery. Stem cell-based models could prove to be a new method for unlocking new clues into what causes anorexia and what can cure it.

Nature versus Zika, who will win?

Zika virus is no longer dominating the news headlines these days compared to 2015 when large outbreaks of the virus in the Southern hemisphere came to a head. However, the threat of Zika-induced birth defects, like microcephaly to pregnant women and their unborn children is no less real or serious two years later. There are still no effective vaccines or antiviral drugs that prevent Zika infection but scientists are working fast to meet this unmet need.

Speaking of which, scientists at UCLA think they might have a new weapon in the war against Zika. Back in 2013, they reported that a natural compound in the body called 25HC was effective at attacking viruses and prevented human cells from being infected by viruses like HIV, Ebola and Hepatitis C.

When the Zika outbreak hit, they thought that this compound could potentially be effective at preventing Zika infection as well. In their new study published in the journal Immunity, they tested a synthetic version of 25HC in animal and primate models, they found that it protected against infection. They also tested the compound on human brain organoids, or mini brains in a dish made from pluripotent stem cells. Brain organoids are typically susceptible to Zika infection, which causes substantial cell damage, but this was prevented by treatment with 25HC.

Left to right: (1) Zika virus (green) infects and destroys the formation of neurons (pink) in human stem cell-derived brain organoids.  (2) 25HC blocks Zika infection and preserves neuron formation in the organoids. (3) Reduced brain size and structure in a Zika-infected mouse brain. (4) 25HC preserves mouse brain size and structure. Image courtesy of UCLA Stem Cell.

A UCLA news release summarized the impact that this research could have on the prevention of Zika infection,

“The new research highlights the potential use of 25HC to combat Zika virus infection and prevent its devastating outcomes, such as microcephaly. The research team will further study whether 25HC can be modified to be even more effective against Zika and other mosquito-borne viruses.”

Harnessing a naturally made weapon already found in the human body to fight Zika could be an alternative strategy to preventing Zika infection.

Gene therapy in stem cells gives hope to bubble-babies.

Last week, an inspiring and touching story was reported by Erin Allday in the San Francisco Chronicle. She featured Ja’Ceon Golden, a young baby not even 6 months old, who was born into a life of isolation because he lacked a properly functioning immune system. Ja’Ceon had a rare disease called severe combined immunodeficiency (SCID), also known as bubble-baby disease.

 

Ja’Ceon Golden is treated by patient care assistant Grace Deng (center) and pediatric oncology nurse Kat Wienskowski. Photo: Santiago Mejia, The Chronicle.

Babies with SCID lack the body’s immune defenses against infectious diseases and are forced to live in a sterile environment. Without early treatment, SCID babies often die within one year due to recurring infections. Bone marrow transplantation is the most common treatment for SCID, but it’s only effective if the patient has a donor that is a perfect genetic match, which is only possible for about one out of five babies with this disease.

Advances in gene therapy are giving SCID babies like Ja’Ceon hope for safer, more effective cures. The SF Chronicle piece highlights two CIRM-funded clinical trials for SCID run by UCLA in collaboration with UCSF and St. Jude Children’s Research Hospital. In these trials, scientists isolate the bone marrow stem cells from SCID babies, correct the genetic mutation causing SCID in their stem cells, and then transplant them back into the patient to give them a healthy new immune system.

The initial results from these clinical trials are promising and support other findings that gene therapy could be an effective treatment for certain genetic diseases. CIRM’s Senior Science Officer, Sohel Talib, was quoted in the Chronicle piece saying,

“Gene therapy has been shown to work, the efficacy has been shown. And it’s safe. The confidence has come. Now we have to follow it up.”

Ja’Ceon was the first baby treated at the UCSF Benioff Children’s Hospital and so far, he is responding well to the treatment. His great aunt Dannie Hawkins said that it was initially hard for her to enroll Ja’Ceon in this trial because she was a partial genetic match and had the option of donating her own bone-marrow to help save his life. In the end, she decided that his involvement in the trial would “open the door for other kids” to receive this treatment if it worked.

Ja’Ceon Golden plays with patient care assistant Grace Deng in a sterile play area at UCSF Benioff Children’s Hospital.Photo: Santiago Mejia, The Chronicle

It’s brave patients and family members like Ja’Ceon and Dannie that make it possible for research to advance from clinical trials into effective treatments for future patients. We at CIRM are eternally grateful for their strength and the sacrifices they make to participate in these trials.

Three people left blind by Florida clinic’s unproven stem cell therapy

Unproven treatment

Unproven stem cell treatments endanger patients: Photo courtesy Healthline

The report makes for chilling reading. Three women, all suffering from macular degeneration – the leading cause of vision loss in the US – went to a Florida clinic hoping that a stem cell therapy would save their eyesight. Instead, it caused all three to go blind.

The study, in the latest issue of the New England Journal of Medicine, is a warning to all patients about the dangers of getting unproven, unapproved stem cell therapies.

In this case, the clinic took fat and blood from the patient, put the samples through a centrifuge to concentrate the stem cells, mixed them together and then injected them into the back of the woman’s eyes. In each case they injected this mixture into both eyes.

Irreparable harm

Within days the women, who ranged in age from 72 to 88, began to experience severe side effects including bleeding in the eye, detached retinas, and vision loss. The women got expert treatment at specialist eye centers to try and undo the damage done by the clinic, but it was too late. They are now blind with little hope for regaining their eyesight.

In a news release Thomas Alibini, one of the lead authors of the study, says clinics like this prey on vulnerable people:

“There’s a lot of hope for stem cells, and these types of clinics appeal to patients desperate for care who hope that stem cells are going to be the answer, but in this case these women participated in a clinical enterprise that was off-the-charts dangerous.”

Warning signs

So what went wrong? The researchers say this clinic’s approach raised a number of “red flags”:

  • First there is almost no evidence that the fat/blood stem cell combination the clinic used could help repair the photoreceptor cells in the eye that are attacked in macular degeneration.
  • The clinic charged the women $5,000 for the procedure. Usually in FDA-approved trials the clinical trial sponsor will cover the cost of the therapy being tested.
  • Both eyes were injected at the same time. Most clinical trials would only treat one eye at a time and allow up to 30 days between patients to ensure the approach was safe.
  • Even though the treatment was listed on the clinicaltrials.gov website there is no evidence that this was part of a clinical trial, and certainly not one approved by the Food and Drug Administration (FDA) which regulates stem cell therapies.

As CIRM’s Abla Creasey told the San Francisco Chronicle’s Erin Allday, there is little evidence these fat stem cells are effective, or even safe, for eye conditions.

“There’s no doubt there are some stem cells in fat. As to whether they are the right cells to be put into the eye, that’s a different question. The misuse of stem cells in the wrong locations, using the wrong stem cells, is going to lead to bad outcomes.”

The study points out that not all projects listed on the Clinicaltrials.gov site are checked to make sure they are scientifically sound and have done the preclinical testing needed to reduce the likelihood they may endanger patients.

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Jeffrey Goldberg

Jeffrey Goldberg, a professor of Ophthalmology at Stanford and the co-author of the study, says this is a warning to all patients considering unproven stem cell therapies:

“There is a lot of very well-founded evidence for the positive potential of stem therapy for many human diseases, but there’s no excuse for not designing a trial properly and basing it on preclinical research.”

There are a number of resources available to people considering being part of a clinical trial including CIRM’s “So You Want to Participate in a Clinical Trial”  and the  website A Closer Look at Stem Cells , which is sponsored by the International Society for Stem Cell Research (ISSCR).

CIRM is currently funding two clinical trials aimed at helping people with vision loss. One is Dr. Mark Humayun’s research on macular degeneration – the same disease these women had – and the other is Dr. Henry Klassen’s research into retinitis pigmentosa. Both these projects have been approved by the FDA showing they have done all the testing required to try and ensure they are safe in people.

In the past this blog has been a vocal critic of the FDA and the lengthy and cumbersome approval process for stem cell clinical trials. We have, and still do, advocate for a more efficient process. But this study is a powerful reminder that we need safeguards to protect patients, that any therapy being tested in people needs to have undergone rigorous testing to reduce the likelihood it may endanger them.

These three women paid $5,000 for their treatment. But the final cost was far greater. We never want to see that happen to anyone ever again.

A Clinical Trial Network Focused on Stem Cell Treatments is Expanding

Geoff Lomax is a Senior Officer of CIRM’s Strategic Initiatives.

California is one of the world-leaders in advancing stem cell research towards treatments and cures for patients with unmet medical needs. California has scientists at top universities and companies conducting cutting edge research in regenerative medicine. It also has CIRM, California’s Stem Cell Agency, which funds promising stem cell research and is advancing stem cell therapies into clinical trials. But the real clincher is that California has something that no one else has: a network of medical centers dedicated to stem cell-based clinical trials for patients. This first-of-its-kind system is called the CIRM Alpha Stem Cell Clinics Network.

Get to Know Our Alpha Clinics

In 2014, CIRM launched its Alpha Stem Cell Clinics Network to accelerate the development and delivery of stem cell treatments to patients. The network consists of three Alpha Clinic sites at UC San Diego, City of Hope in Duarte, and a joint clinic between UC Los Angeles and UC Irvine. Less than three years since its inception, the Alpha Clinics are conducting 34 stem cell clinical trials for a diverse range of diseases such as cancer, heart disease and sickle cell anemia. You can find a complete list of these clinical trials on our Alpha Clinics website. Below is an informational video about our Alpha Clinics Network.

So far, hundreds of patients have been treated at our Alpha Clinics. These top-notch medical centers use CIRM-funding to build teams specialized in overseeing stem cell trials. These teams include patient navigators who provided in-depth information about clinical trials to prospective patients and support them during their treatment. They also include pharmacists who work with patients’ cells or manufactured stem cell-products before the therapies are given to patients. And lastly, let’s not forget the doctors and nurses that are specially trained in the delivery of stem cell therapies to patients.

The Alpha Clinics Network also offers resources and tools for clinical trial sponsors, the people responsible for conducting the trials. These include patient education and recruitment tools and access to over 20 million patients in California to support successful recruitment. And because the different clinical trial sites are in the same network, sponsors can benefit from sharing the same approval measures for a single trial at multiple sites.

Looking at the big picture, our Alpha Clinics Network provides a platform where patients can access the latest stem cell treatments, and sponsors can access expert teams at multiple medical centers to increase the likelihood that their trial succeeds.

The Alpha Clinics Network is expanding

This collective expertise has resulted in a 3-fold (from 12 to 36 – two trials are being conducted at two sites) increase in the number of stem cell clinical trials at the Alpha Clinic sites since the Network’s inception. And the number continues to rise every quarter. Given this impressive track record, CIRM’s Board voted in February to expand our Alpha Clinics Network. The Board approved up to $16 million to be awarded to two additional medical centers ($8 million each) to create new Alpha Clinic sites and work with the current Network to accelerate patient access to stem cell treatments.

CIRM’s Chairman Jonathan Thomas explained,

Jonathan Thomas

“We laid down the foundation for conducting high quality stem cell trials when we started this network in 2014. The success of these clinics in less than three years has prompted the CIRM Board to expand the Network to include two new trial sites. With this expansion, CIRM is building on the current network’s momentum to establish new and better ways of treating patients with stem cell-based therapies.”

The Alpha Clinics Network plays a vital role in CIRM’s five-year strategic plan to fund 50 new clinical trials by 2020. In fact, the Alpha Clinic Network supports clinical trials funded by CIRM, industry sponsors and other sources. Thus, the Network is on track to becoming a sustainable resource to deliver stem cell treatments indefinitely.

In addition to expanding CIRM’s Network, the new sites will develop specialized programs to train doctors in the design and conduct of stem cell clinical trials. This training will help drive the development of new stem cell therapies at California medical centers.

Apply to be one our new Alpha Clinics!

For the medical centers interested in joining the CIRM Alpha Stem Cell Clinics Network, the deadline for applications is May 15th, 2017. Details on this funding opportunity can be found on our funding page.

The CIRM Team looks forward to working with prospective applicants to address any questions. The Alpha Stem Cell Clinics Network will also be showcasing it achievement at its Second Annual Symposium, details may be found on the City of Hope Alpha Clinics website.

City of Hope Medical Center and Alpha Stem Cell Clinic


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License to heal: UC Davis deal looks to advance stem cell treatment for bone loss and arthritis

Nancy Lane

Wei Yao and Nancy Lane of UC Davis: Photo courtesy UC Davis

There are many challenges in taking even the most promising stem cell treatment and turning it into a commercial product approved by the Food and Drug Administration (FDA). One of the biggest is expertise. The scientists who develop the therapy may be brilliant in the lab but have little experience or expertise in successfully getting their work through a clinical trial and ultimately to market.

That’s why a team at U.C. Davis has just signed a deal with a startup company to help them move a promising stem cell treatment for arthritis, osteoporosis and fractures out of the lab and into people.

The licensing agreement combines the business acumen of Regenerative Arthritis and Bone Medicine (RABOME) with the scientific chops of the UC Davis team, led by Nancy Lane and Wei Yao.

They plan to test a hybrid molecule called RAB-001 which has shown promise in helping direct mesenchymal stem cells (MSCs) – these are cells typically found in the bone marrow and fat tissue – to help stimulate bone growth and increase existing bone mass and strength. This can help heal people suffering from conditions like osteoporosis or hard to heal fractures. RAB-001 has also shown promise in reducing inflammation and so could prove helpful in treating people with inflammatory arthritis.

Overcoming problems

In a news article on the UC Davis website, Wei Yao, said RAB-001 seems to solve a problem that has long puzzled researchers:

“There are many stem cells, even in elderly people, but they do not readily migrate to bone.  Finding a molecule that attaches to stem cells and guides them to the targets we need provides a real breakthrough.”

The UC Davis team already has approval to begin a Phase 1 clinical trial to test this approach on people with osteonecrosis, a disease caused by reduced blood flow to bones. CIRM is funding this work.

The RABOME team also hopes to test RAB-001 in clinical trials for healing broken bones, osteoporosis and inflammatory arthritis.

CIRM solution

To help other researchers overcome these same regulatory hurdles in developing stem cell therapies CIRM created the Stem Cell Center with QuintilesIMS, a leading integrated information and technology-enabled healthcare service provider that has deep experience and therapeutic expertise. The Stem Cell Center will help researchers overcome the challenges of manufacturing and testing treatments to meet FDA standards, and then running a clinical trial to test that therapy in people.

Partnering with the best to help find cures for rare diseases

As a state agency we focus most of our efforts and nearly all our money on California. That’s what we were set up to do. But that doesn’t mean we don’t also look outside the borders of California to try and find the best research, and the most promising therapies, to help people in need.

Today’s meeting of the CIRM Board was the first time we have had a chance to partner with one of the leading research facilities in the country focusing on children and rare diseases; St. Jude Children’s Researech Hospital in Memphis, Tennessee.

a4da990e3de7a2112ee875fc784deeafSt. Jude is getting $11.9 million to run a Phase I/II clinical trial for x-linked severe combined immunodeficiency disorder (SCID), a catastrophic condition where children are born without a functioning immune system. Because they are unable to fight off infections, many children born with SCID die in the first few years of life.

St. Jude is teaming up with researchers at the University of California, San Francisco (UCSF) to genetically modify the patient’s own blood stem cells, hopefully creating a new blood system and repairing the damaged immune system. St. Jude came up with the method of doing this, UCSF will treat the patients. Having that California component to the clinical trial is what makes it possible for us to fund this work.

This is the first time CIRM has funded work with St. Jude and reflects our commitment to moving the most promising research into clinical trials in people, regardless of whether that work originates inside or outside California.

The Board also voted to fund researchers at Cedars-Sinai to run a clinical trial on ALS or Lou Gehrig’s disease. Like SCID, ALS is a rare disease. As Randy Mills, our President and CEO, said in a news release:

CIRM CEO and President, Randy Mills.

CIRM CEO and President, Randy Mills.

“While making a funding decision at CIRM we don’t just look at how many people are affected by a disease, we also look at the severity of the disease on the individual and the potential for impacting other diseases. While the number of patients afflicted by these two diseases may be small, their need is great. Additionally, the potential to use these approaches in treating other disease is very real. The underlying technology used in treating SCID, for example, has potential application in other areas such as sickle cell disease and HIV/AIDS.”

We have written several blogs about the research that cured children with SCID.

The Board also approved funding for a clinical trial to develop a treatment for type 1 diabetes (T1D). This is an autoimmune disease that affects around 1.25 million Americans, and millions more around the globe.

T1D is where the body’s own immune system attacks the cells that produce insulin, which is needed to control blood sugar levels. If left untreated it can result in serious, even life-threatening, complications such as vision loss, kidney damage and heart attacks.

Researchers at Caladrius Biosciences will take cells, called regulatory T cells (Tregs), from the patient’s own immune system, expand the number of those cells in the lab and enhance them to make them more effective at preventing the autoimmune attack on the insulin-producing cells.

The focus is on newly-diagnosed adolescents because studies show that at the time of diagnosis T1D patients usually have around 20 percent of their insulin-producing cells still intact. It’s hoped by intervening early the therapy can protect those cells and reduce the need for patients to rely on insulin injections.

David J. Mazzo, Ph.D., CEO of Caladrius Biosciences, says this is hopeful news for people with type 1 diabetes:

David Mazzo

David Mazzo

“We firmly believe that this therapy has the potential to improve the lives of people with T1D and this grant helps us advance our Phase 2 clinical study with the goal of determining the potential for CLBS03 to be an effective therapy in this important indication.”

 


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The power of the patient’s voice: how advocates shape clinical trials and give hope to those battling deadly diseases

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The Stack family: L to R Alex, Natalie, Nancy & Jeff

Tennis great Martina Navratilova was once being interviewed about what made her such a great competitor and she said it was all down to commitment. When pressed she said “the difference between involvement and commitment is like ham and eggs; the chicken is involved but the pig is committed.”

That’s how I feel about the important role that patients and patient advocates play in the work that we do at CIRM. Those of us who work here are involved. The patients and patient advocates are committed. This isn’t just their life’s work;  it’s their life.

I was reminded of that last week when I had the privilege of talking with Nancy Stack, the Patient Representative on a Clinical Advisory Panel (CAP) we have created for a program to treat cystinosis. She has an amazing story to tell. But before we get to that I have to do a little explaining.

Cystinosis is a rare disease, affecting maybe only 2,000 people worldwide, that usually strikes children before they are two years old and can lead to end stage kidney failure before their tenth birthday. Current treatments are limited, which is why the average life expectancy for someone with this is only around 27 years.

When we fund a project that is already in, or hoping to be in, a clinical trial we create a CAP to help assist the team behind the research. The CAP consists of a CIRM Science Officer, an independent scientific expert in this case for cystinosis, and a Patient Representative.

The patient’s voice

The Patient Representative’s role is vital because they can help the researchers understand the needs of the patient and take those needs into account when designing the trial. In the past, many researchers had little contact with patients and so designed the trial around their own needs. The patients had to fit into that model. We think it should be the other way around; that the model should fit the patients. The Patient Representatives help us make that happen.

Nancy Stack did just that. At the first meeting of the CAP she showed up with a list of 38 questions that she and other families with cystinosis had come up with for the researchers. They went from the blunt – “Will I die from the treatment” – to the practical –  “How will children/teens keep up with school during the process?” – and included a series of questions from a 12-year old girl with the disease – “Will I lose my hair because I’ve been growing it out for a long time? Will I feel sick? Will it hurt?”

Nancy says the questions are not meant to challenge the researcher, in this case U.C. San Diego’s Stephanie Cherqui, but to ensure that if the trial is given the go-ahead by the US Food and Drug Administration (FDA) that every patient who signs up for it knows exactly what they are getting into. That’s particularly important because many of those could be children or teenagers.

Fully informed

“As parents we know the science is great and is advancing, but we have real people who are going to go through this treatment so we have a responsibility to know what will it mean to them. Patients know they could die of the disease and so this research has real world implications for them.”

“I think without this, without allowing the patients voice to be heard, you would have a hard time recruiting patients for this kind of clinical trial.”

Nancy says not only was Dr. Cherqui not surprised by the questions, she welcomed them. Dr. Cherqui has been supported and funded by the Cystinosis Research Foundation for years and Nancy says she regards the patients and patient advocates as partners in this journey:

“She knows we are not challenging her, we’re supporting her and helping her cover every aspect of the research to help make it work.”

Nancy became committed to finding a cure for cystinosis when her daughter, Natalie, was diagnosed with the condition when she was just 7 months old. The family were handed a pamphlet titled “What to do when your child has a terminal disease” and told there was no cure.

Birthday wish

In 2003, on the eve of her 12th birthday, Nancy asked Natalie what her wish was for her birthday. She wrote on a napkin “to have my disease go away forever.” The average life expectancy for people with cystinosis at that point was 18. Nancy told her husband “We have to do something.”

They launched the Cystinosis Research Foundation and a few weeks later they held their first fundraiser. That first year they raised $427,000, an impressive amount for such a rare disease. Last year they raised $4.94 million. Every penny of that $4.94 million goes towards research, making them the largest funders of cystinosis research in the world.

“We learned that for there to be hope there has to be research, and to do research we needed to raise funds. Without that we knew our children would not survive this disease.”

Natalie is now 26, a graduate of Georgetown and USC, and about to embark on a career in social work. Nancy knows many others are not so fortunate:

“Every year we lose some of our adults, even some of our teens, and that is unbelievably hard. Those other children, wherever they may live, they are my children too. We are all connected to each other and that’s what motivates me every day. Having a child with this disease means that time is running out and there must be a commitment to work hard every day to find a cure, and never giving up until you do.”

That passion for the cause, that compassion for others and determination to help others makes the Patient Representative on the CAP so important. They are a reminder that we all need to work as hard as we can, as fast as we can, and do everything we can to help these trials succeed.

And we are committed to doing that.


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Curing the Incurable through Definitive Medicine

“Curing the Incurable”. That was the theme for the first annual Center for Definitive and Curative Medicine (CDCM) Symposium held last week at Stanford University, in Palo Alto, California.

The CDCM is a joint initiative amongst Stanford Healthcare, Stanford Children’s Health and the Stanford School of Medicine. Its mission is to foster an environment that accelerates the development and translation of cell and gene therapies into clinical trials.

The research symposium focused on “the exciting first-in-human cell and gene therapies currently under development at Stanford in bone marrow, skin, cardiac, neural, pancreatic and neoplastic diseases.” These talks were organized into four different sessions: cell therapies for neurological disorders, stem cell-derived tissue replacement therapies, genome-edited cell therapies and anti-cancer cell-based therapies.

A few of the symposium speakers are CIRM-funded grantees, and we’ll briefly touch on their talks below.

Targeting cancer

The keynote speaker was Irv Weissman, who talked about hematopoietic or blood-forming stem cells and their value as a cell therapy for patients with blood disorders and cancer. One of the projects he discussed is a molecule called CD47 that is found on the surface of cancer cells. He explained that CD47 appears on all types of cancer cells more abundantly than on normal cells and is a promising therapeutic target for cancer.

Irv Weissman

Irv Weissman

“CD47 is the first gene whose overexpression is common to all cancer. We know it’s molecular mechanism from which we can develop targeted therapies. This would be impossible without collaborations between clinicians and scientists.”

 

At the end of his talk, Weissman acknowledged the importance of CIRM’s funding for advancing an antibody therapeutic targeting CD47 into a clinical trial for solid cancer tumors. He said CIRM’s existence is essential because it “funds [stem cell-based] research through the [financial] valley of death.” He further explained that CIRM is the only funding entity that takes basic stem cell research all the way through the clinical pipeline into a therapy.

Improving bone marrow transplants

judith shizuru

Judith Shizuru

Next, we heard a talk from Judith Shizuru on ways to improve current bone-marrow transplantation techniques. She explained how this form of stem cell transplant is “the most powerful form of cell therapy out there, for cancers or deficiencies in blood formation.” Inducing immune system tolerance, improving organ transplant outcomes in patients, and treating autoimmune diseases are all applications of bone marrow transplants. But this technique also carries with it toxic and potentially deadly side effects, including weakening of the immune system and graft vs host disease.

Shizuru talked about her team’s goal of improving the engraftment, or survival and integration, of bone marrow stem cells after transplantation. They are using an antibody against a molecule called CD117 which sits on the surface of blood stem cells and acts as an elimination signal. By blocking CD117 with an antibody, they improved the engraftment of bone marrow stem cells in mice and also removed the need for chemotherapy treatment, which is used to kill off bone marrow stem cells in the host. Shizuru is now testing her antibody therapy in a CIRM-funded clinical trial in humans and mentioned that this therapy has the potential to treat a wide variety of diseases such as sickle cell anemia, leukemias, and multiple sclerosis.

Tackling stroke and heart disease

img_1327We also heard from two CIRM-funded professors working on cell-based therapies for stroke and heart disease. Gary Steinberg’s team is using human neural progenitor cells, which develop into cells of the brain and spinal cord, to treat patients who’ve suffered from stroke. A stroke cuts off the blood supply to the brain, causing the death of brain cells and consequently the loss of function of different parts of the body.  He showed emotional videos of stroke patients whose function and speech dramatically improved following the stem cell transplant. One of these patients was Sonia Olea, a young woman in her 30’s who lost the ability to use most of her right side following her stroke. You can read about her inspiring recover post stem cell transplant in our Stories of Hope.

Dr. Joe Wu. (Image Source: Sean Culligan/OZY)

Dr. Joe Wu. (Image Source: Sean Culligan/OZY)

Joe Wu followed with a talk on adult stem cell therapies for heart disease. His work, which is funded by a CIRM disease team grant, involves making heart cells called cardiomyocytes from human embryonic stem cells and transplanting these cells into patient with end stage heart failure to improve heart function. His team’s work has advanced to the point where Wu said they are planning to file for an investigational new drug (IND) application with the US Food and Drug Administration (FDA) in six months. This is the crucial next step before a treatment can be tested in clinical trials. Joe ended his talk by making an important statement about expectations on how long it will take before stem cell treatments are available to patients.

He said, “Time changes everything. It [stem cell research] takes time. There is a lot of promise for the future of stem cell therapy.”

A ‘Call to Action’ for change at the FDA

hd

It’s bad enough to have to battle a debilitating and ultimately deadly disease like Huntington’s disease (HD). But it becomes doubly difficult and frustrating when you feel that the best efforts to develop a therapy for HD are running into a brick wall.

That’s how patients and patient advocates working on HD feel as they see the Food and Drug Administration (FDA) throw up what they feel are unnecessary obstacles in the way of promising research.

So the group Help 4HD International has decided to push back, launching an online campaign to get its supporters to pressure the FDA into taking action. Any action.

Posing the question “Does the FDA understand that time is something we simply don’t have?” Help 4HD is urging people to write to the FDA:

“We have heard the FDA say they feel like our loved ones have quality of life at the end stages of HD. We have heard them say people with HD get to live for 20 years after diagnosis. It seems like the FDA doesn’t understand what we are having to live with generation after generation. We have seen HD research die because the researcher couldn’t get an IND (Investigational New Drug, or approval to put a new drug into clinical trials) from the FDA. We have seen trials that should be happening here in the USA move to other countries because of this. We have seen the FDA continue to put up delays and roadblocks. We are lucky to have amazing research going on for HD/JHD (juvenile HD) right now, but what is that research worth if the FDA doesn’t let it go into clinical trials? Drug development is a business and costs millions of dollars. If the FDA continues to refuse INDs, the fear is that companies will stop investing in HD research. This is a fate that we can’t let happen! We need to write to the FDA and let them know our frustrations and also help them understand our disease better.”

The group has drafted a sample letter for people to use or adapt as they see fit. They’ve even provided them with the address to mail the letter to. In short, they are making it as easy as possible to get as many people as possible to write to the FDA and ask for help.

The HD community is certainly not the only one frustrated at the FDA’s  glacial pace of approval of for clinical trials. That frustration is one of many reasons why Congress passed the 21st Century Cures Act late last year. That’s also the reason why we started our Stem Cell Champions campaign, to get the FDA to create a more efficient, but no less safe, approval process.

Several of our most active Stem Cell Champions – like Frances Saldana, Judy Roberson and Katie Jackson – are members of the HD Community. Last May several members of the CIRM Team attended the HD-Care Conference, held to raise awareness about the unmet medical needs of this community. We blogged about it here.

While this call to action comes from the HD community it may serve as a template for other organizations and communities. Many have the same frustrations at the slow pace of approval of therapies for clinical trials.

We are hoping the 21st Century Cures Act will lead to the desired changes at the FDA. But until we see proof that’s the case we understand and support the sense of urgency that the HD community has. They don’t have the luxury of time.