jCyte gets FDA go-ahead for Fast Track review process of Retinitis Pigmentosa stem cell therapy

21 century cures

When the US Congress approved, and President Obama signed into law, the 21st Century Cures Act last year there was guarded optimism that this would help create a more efficient and streamlined, but no less safe, approval process for the most promising stem cell therapies.

Even so many people took a wait and see approach, wanting a sign that the Food and Drug Administration (FDA) would follow the recommendations of the Act rather than just pay lip service to it.

This week we saw encouraging signs that the FDA is serious when it granted Regenerative Medicine Advanced Therapy (RMAT) status to the CIRM-funded jCyte clinical trial for a rare form of blindness. This is a big deal because RMAT seeks to accelerate approval for stem cell therapies that demonstrate they can help patients with unmet medical needs.

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jCyte co-founder Dr. Henry Klassen

jCyte’s work is targeting retinitis pigmentosa (RP), a genetic disease that slowly destroys the cells in the retina, the part of the eye that converts light into electrical signals which the brain then interprets as vision. At first people with RP lose their night and peripheral vision, then the cells that help us see faces and distinguish colors are damaged. RP usually strikes people in their teens and, by the time they are 40, many people are legally blind.

jCyte’s jCell therapy uses what are called retinal progenitor cells, injected into the eye, which then release protective factors to help repair and rescue diseased retinal cells. The hope is this will stop the disease’s progression and even restore some vision to people with RP.

Dr. Henry Klassen, jCyte’s co-founder and a professor at UC Irvine, was understandably delighted by the designation. In a news release, he said:

“This is uplifting news for patients with RP. At this point, there are no therapies that can help them avoid blindness. We look forward to working with the FDA to speed up the clinical development of jCell.”

FDA

On the FDA’s blog – yes they do have one – it says researchers:

“May obtain the RMAT designation for their drug product if the drug is intended to treat serious or life-threatening diseases or conditions and if there is preliminary clinical evidence indicating that the drug has the potential to address unmet medical needs for that disease or condition. Sponsors of RMAT-designated products are eligible for increased and earlier interactions with the FDA, similar to those interactions available to sponsors of breakthrough-designated therapies. In addition, they may be eligible for priority review and accelerated approval.”

Paul Bresge

jCyte CEO Paul Bresge

jCyte is one of the first to get this designation, a clear testimony to the quality of the work done by Dr. Klassen and his team. jCyte CEO Paul Bresge says it may help speed up their ability to get this treatment to patients.

 

“We are gratified by the FDA’s interest in the therapeutic potential of jCell and greatly appreciate their decision to provide extra support. We are seeing a lot of momentum with this therapy. Because it is well-tolerated and easy to administer, progress has been rapid. I feel a growing sense of excitement among patients and clinicians. We look forward to getting this critical therapy over the finish line as quickly as possible.”

Regular readers of this blog will already be familiar with the story of Rosie Barrero, one of the first group of people with RP who got the jCell therapy. Rosie says it has helped restore some vision to the point where she is now able to read notes she wrote ten years ago, distinguish colors and, best of all, see the faces of her children.

RMAT is no guarantee the therapy will be successful. But if the treatment continues to show promise, and is safe, it could mean faster access to a potentially life-changing therapy, one that could ultimately rescue many people from a lifetime of living in the dark.

 

 

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

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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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Stem Cell Stories That Caught Our Eye: Free Patient Advocate Event in San Diego, and new clues on how to fix muscular dystrophy and Huntington’s disease

UCSD Patient Advocate mtg instagram

Stem cell research is advancing so fast that it’s sometimes hard to keep up. That’s one of the reasons we have our Friday roundup, to let you know about some fascinating research that came across our desk during the week that you might otherwise have missed.

Of course, another way to keep up with the latest in stem cell research is to join us for our free Patient Advocate Event at UC San Diego next Thursday, April 20th from 12-1pm.  We are going to talk about the progress being made in stem cell research, the problems we still face and need help in overcoming, and the prospects for the future.

We have four great speakers:

  • Catriona Jamieson, Director of the CIRM UC San Diego Alpha Stem Cell Clinic and an expert on cancers of the blood
  • Jonathan Thomas, PhD, JD, Chair of CIRM’s Board
  • Jennifer Briggs Braswell, Executive Director of the Sanford Stem Cell Clinical Center
  • David Higgins, Patient Advocate for Parkinson’s on the CIRM Board

We will give updates on the exciting work taking place at UCSD and the work that CIRM is funding. We have also set aside some time to get your thoughts on how we can improve the way we work and, of course, answer your questions.

What: Stem Cell Therapies and You: A Special Patient Advocate Event

When: Thursday, April 20th 12-1pm

Where: The Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037

Why: Because the people of California have a right to know how their money is helping change the face of regenerative medicine

Who: This event is FREE and open to everyone.

We have set up an EventBrite page for you to RSVP and let us know if you are coming. And, of course, feel free to share this with anyone you think might be interested.

This is the first of a series of similar Patient Advocate Update meetings we plan on holding around California this year. We’ll have news on other locations and dates shortly.

 

Fixing a mutation that causes muscular dystrophy (Karen Ring)

It’s easy to take things for granted. Take your muscles for instance. How often do you think about them? (Don’t answer this if you’re a body builder). Daily? Monthly? I honestly don’t think much about my muscles unless I’ve injured them or if they’re sore from working out.

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Heart muscle cells (green) that don’t have dystrophin protein (Photo; UT Southwestern)

But there are people in this world who think about their muscles or their lack of them every day. They are patients with a muscle wasting disease called Duchenne muscular dystrophy (DMD). It’s the most common type of muscular dystrophy, and it affects mainly young boys – causing their muscles to progressively weaken to the point where they cannot walk or breathe on their own.

DMD is caused by mutations in the dystrophin gene. These mutations prevent muscle cells from making dystrophin protein, which is essential for maintaining muscle structure. Scientists are using gene editing technologies to find and fix these mutations in hopes of curing patients of DMD.

Last year, we blogged about a few of these studies where different teams of scientists corrected dystrophin mutations using CRISPR/Cas9 gene editing technology in human cells and in mice with DMD. One of these teams has recently followed up with a new study that builds upon these earlier findings.

Scientists from UT Southwestern are using an alternative form of the CRISPR gene editing complex to fix dystrophin mutations in both human cells and mice. This alternative CRISPR complex makes use of a different cutting enzyme, Cpf1, in place of the more traditionally used Cas9 protein. It’s a smaller protein that the scientists say can get into muscle cells more easily. Cpf1 also differs from Cas9 in what DNA nucleotide sequences it recognizes and latches onto, making it a new tool in the gene editing toolbox for scientists targeting DMD mutations.

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Gene-edited heart muscle cells (green) that now express dystrophin protein (Photo: UT Southwestern)

Using CRISPR/Cpf1, the scientists corrected the most commonly found dystrophin mutation in human induced pluripotent stem cells derived from DMD patients. They matured these corrected stem cells into heart muscle cells in the lab and found that they expressed the dystrophin protein and functioned like normal heart cells in a dish. CRISPR/Cpf1 also corrected mutations in DMD mice, which rescued dystrophin expression in their muscle tissues and some of the muscle wasting symptoms caused by the disease.

Because the dystrophin gene is one of the longest genes in our genome, it has more locations where DMD-causing mutations could occur. The scientists behind this study believe that CRISPR/Cpf1 offers a more flexible tool for targeting different dystrophin mutations and could potentially be used to develop an effective gene therapy for DMD.

Senior author on the study, Dr. Eric Olson, provided this conclusion about their research in a news release by EurekAlert:

“CRISPR-Cpf1 gene-editing can be applied to a vast number of mutations in the dystrophin gene. Our goal is to permanently correct the underlying genetic causes of this terrible disease, and this research brings us closer to realizing that end.”

 

A cellular traffic jam is the culprit behind Huntington’s disease (Todd Dubnicoff)

Back in the 1983, the scientific community cheered the first ever mapping of a genetic disease to a specific area on a human chromosome which led to the isolation of the disease gene in 1993. That disease was Huntington’s, an inherited neurodegenerative disorder that typically strikes in a person’s thirties and leads to death about 10 to 15 years later. Because no effective therapy existed for the disease, this discovery of Huntingtin, as the gene was named, was seen as a critical step toward a better understand of Huntington’s and an eventual cure.

But flash forward to 2017 and researchers are still foggy on how mutations in the Huntingtin gene cause Huntington’s. New research, funded in part by CIRM, promises to clear some things up. The report, published this week in Neuron, establishes a connection between mutant Huntingtin and its impact on the transport of cell components between the nucleus and cytoplasm.

Roundup Picture1

The pores in the nuclear envelope allows proteins and molecules to pass between a cell’s nucleus and it’s cytoplasm. Image: Blausen.com staff (2014).

To function smoothly, a cell must be able to transport proteins and molecules in and out of the nucleus through holes called nuclear pores. The research team – a collaboration of scientists from Johns Hopkins University, the University of Florida and UC Irvine – found that in nerve cells, the mutant Huntingtin protein clumps up and plays havoc on the nuclear pore structure which leads to cell death. The study was performed in fly and mouse models of HD, in human HD brain samples as well as HD patient nerve cells derived with the induced pluripotent stem cell technique – all with this same finding.

Roundup Picture2

Huntington’s disease is caused by the loss of a nerve cells called medium spiny neurons. Image: Wikimedia commons

By artificially producing more of the proteins that make up the nuclear pores, the damaging effects caused by the mutant Huntingtin protein were reduced. Similar results were seen using drugs that help stabilize the nuclear pore structure. The implications of these results did not escape George Yohrling, a senior director at the Huntington’s Disease Society of America, who was not involved in the study. Yohrling told Baltimore Sun reporter Meredith Cohn:

“This is very exciting research because we didn’t know what mutant genes or proteins were doing in the body, and this points to new areas to target research. Scientists, biotech companies and pharmaceutical companies could capitalize on this and maybe develop therapies for this biological process”,

It’s important to temper that excitement with a reality check on how much work is still needed before the thought of clinical trials can begin. Researchers still don’t understand why the mutant protein only affects a specific type of nerve cells and it’s far from clear if these drugs would work or be safe to use in the context of the human brain.

Still, each new insight is one step in the march toward a cure.

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


Related Links:

How stem cells are helping change the face of medicine, one pioneering patient at a time

One of the many great pleasures of my job is that I get to meet so many amazing people. I get to know the researchers who are changing the face of medicine, but even more extraordinary are the people who are helping them do it, the patients.

Attacking Cancer

Karl

Karl Trede

It’s humbling to meet people like Karl Trede from San Jose, California. Karl is a quiet, witty, unassuming man who when the need arose didn’t hesitate to put himself forward as a medical pioneer.

Diagnosed with throat cancer in 2006, Karl underwent surgery to remove the tumor. Several years later, his doctors told him it had returned, only this time it had spread to his lungs. They told him there was no effective treatment. But there was something else.

“One day the doctor said we have a new trial we’re going to start, would you be interested? I said “sure”. I don’t believe I knew at the time that I was going to be the first one, but I thought I’d give it a whirl.”

Karl was Patient #1 in a clinical trial at Stanford University that was using a novel approach to attack cancer stem cells, which have the ability to evade standard anti-cancer treatments and cause the tumors to regrow. The team identified a protein, called CD47, that sits on the surface of cancer stem cells and helps them evade being gobbled up and destroyed by the patient’s own immune system. They dubbed CD47 the “don’t eat me” signal and created an antibody therapy they hoped would block the signal, leaving the cancer and the cancer stem cells open to attack by the immune system.

The team did pre-clinical testing of the therapy, using mice to see if it was safe. Everything looked hopeful. Even so, this was still the first time it was being tested in a human. Karl said that didn’t bother him.

“It was an experience for me, it was eye opening. I wasn’t real concerned about being the first in a trial never tested in people before. I said we know that there’s no effective treatment for this cancer, it’s not likely but it’s possible that this could be the one and if nothing else, if it doesn’t do anything for me hopefully it does something so they learn for others.”

It’s that kind of selflessness that is typical of so many people who volunteer for clinical trials, particularly Phase 1 trials, where a treatment is often being tried in people for the first time ever. In these trials, the goal is to make sure the approach is safe, so patients are given a relatively small dose of the therapy (cells or drugs) and told ahead of time it may not do any good. They’re also told that there could be some side effects, potentially serious, even life-threatening ones. Still, they don’t hesitate.

Improving vision

Rosie Barrero certainly didn’t hesitate when she got a chance to be part of a clinical trial testing the use of stem cells to help people with retinitis pigmentosa, a rare progressive disease that destroys a person’s vision and ultimately leaves them blind.

Rosalinda Barrero

Rosie Barrero

“I was extremely excited about the clinical trial. I didn’t have any fear or trepidation about it, I would have been happy being #1, and I was #6 and that was fine with me.”

 

Rosie had what are called retinal progenitor cells injected into her eye, part of a treatment developed by Dr. Henry Klassen at the University of California, Irvine. The hope was that those cells would help repair and perhaps even replace the light-sensing cells damaged by the disease.

Following the stem cell treatment, gradually Rosie noticed a difference. It was small things at first, like being able to make out the colors of cups in her kitchen cupboard, or how many trash cans were outside their house.

“I didn’t expect to see so much, I thought it would be minor, and it is minor on paper but it is hard to describe the improvement. It’s visible, it’s visible improvement.”

These are the moments that researchers like Henry Klassen live for, and have worked so tirelessly for. These are the moments that everyone at CIRM dreams of, when the work we have championed, supported and funded shows it is working, shows it is changing people’s lives.

One year ago this month our governing Board approved a new Strategic Plan, a detailed roadmap of where we want to go in the coming years. The plan laid out some pretty ambitious goals, such as funding 50 new clinical trials in the next 5 years, and at our Board meeting next week we’ll report on how well we are doing in terms of hitting those targets.

People like Karl and Rosie help motivate us to keep trying, to keep working as hard as we can, to achieve those goals. And if ever we have a tough day, we just have to remind ourselves of what Rosie said when she realized she could once again see her children.

“Seeing their faces. It’s pretty incredible. I always saw them with my heart so I just adore them, but now I can see them with my eye.”


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A patient perspective on how stem cells could give a second vision to the blind

October is Blindness Awareness month. In honor of the patients who suffer from diseases of blindness and of the scientists and doctors who work tirelessly to develop treatments and cures for these diseases, we are featuring an interview with Kristin Macdonald, a woman who is challenged by Retinitis Pigmentosa (RP).

RP is a genetically inherited disease that affects the photoreceptors at the back of the eye in an area called the retina. It’s a hard disease to diagnose because the first signs are subtle. Patients slowly lose their peripheral vision and ability to see well at night. As the disease progresses, the window of sight narrows and patients experience “tunnel vision”. Eventually, they become totally blind. Currently, there is no treatment for RP, but stem cell research might offer a glimmer of hope.

Kristin MacDonald

Kristin MacDonald

Kristin Macdonald was the first patient treated in a CIRM-funded stem cell trial for RP run by Dr. Henry Klassen at UC Irvine. She is a patient advocate and inspirational speaker for the blind and visually impaired, and is also a patient ambassador for Americans for Cures. Kristin is an amazing woman who hasn’t let RP prevent her from living her life. It was my pleasure to interview her to learn more about her life’s vision, her experience in CIRM’s RP trial, and her thoughts on patient advocacy and the importance of stem cell research.


Q: Tell us about your experience with being diagnosed with RP?

I was officially diagnosed with RP at 31. RP is a very difficult thing to diagnose, and I had to go through a series of doctors before we figured it out. The signs were there in my mid-to-late twenties, but unfortunately I didn’t really know what they were.

Being diagnosed with RP was really surprising to me. I grew up riding horses and doing everything. I had 20/20 vision and didn’t need any reading glasses. I started getting these night vision symptoms in my mid-to-late 20s in New York when I was in Manhattan. It was then that I started tripping, falling and getting clumsy. But I didn’t know what was happening and I was having such a great time with my life that I just denied it. I didn’t want to acknowledge that anything was wrong.

So I moved out to Los Angeles to pursue an acting and television career, and I just kept ignoring that thing in the brain that says “something’s wrong”. By the time I broke my arm for the second time, I had to go to see a doctor. And that’s when they diagnosed me.

Q: How did you boost yourself back up after being diagnosed with RP?

RP doesn’t come with an instruction booklet. It’s a very gradual adjustment emotionally, physically and spiritually. The first thing I did was to get out of denial, which was a really scary place to be because you can break your leg that way. You have to acknowledge what’s happening in life otherwise you’ll never get anywhere or past anything. That was my first stage of getting over denial. As I slowly started to accept things, I learned to live in the moment, which in a way is a big thing in life because we should all be living for today.

I think the fear of someone telling you that you’re going to go into the dark when you’ve always lived your life in the light can be overwhelming at times. I used to go to the mall and sometimes a door to a store would be gone or an elevator that I used to see is gone. What I did to deal with these fears and changes was to become as proactive as possible. I enlisted all of the best people around me in the business. I started doing charitable work for the Center for the Partially Sighted and for the Foundation for Fighting Blindness. I sat on the board of AIRSLA.org, an internet radio service for the blind and visually impaired, where I still do my radio show. Through that, I met other people who were going through the same type of thing and would come into my home to teach me independent living skills.

I remember the first day when an independent living counselor from the Center for the Partially Sighted came to my house and said we have to check in and see what your adjustment to blindness is like. Those words cut through me. “Adjustment to blindness”. It felt like I was going to prison, that’s how it felt like to me back then. But I am so glad I reached out to the Center for the Partially Sighted because they gave me invaluable instructions on how to function as a blind person. They helped me realize I could really live a good life and be whole, and that blindness would never define me.

I also worked a lot on my spiritual side. I read a lot of positive thinking books and found comfort in my faith in god and the support from my family, friends and my boyfriend. I can’t even enumerate how good they’ve been to me.

Q: How has being blind impacted your ability to do the things you love?

I’m a very social person, so giving up my car and suddenly being confined at night was crushing to me. And we didn’t have Uber back then! During that time, I had to learn how to lead a full life socially. I still love to do salsa dancing but it’s tricky. If I stand on the sidelines, some of the dancers will pass you by because they don’t know you’re blind. I also learned how to horseback ride and swim in the ocean – just a different way. I go in the water on a surf leash. Or I ride around the ring with my best friend guiding me.

Kristin loves to ride horses.

Kristin doesn’t let being mostly blind stop her from riding horses.

Q: What treatments have you had for RP?

I investigated just about everything that was out there. [Laughs] After I was diagnosed, I became very proactive to find treatments. But after a while, I became discouraged because these treatments either didn’t work or still needed time for the FDA to give approval.

I did participate in a study nine years ago and had genetically modified cells put into my eye. I had two surgeries: one to put the cells in and one to take them out because the treatment hadn’t done anything. I didn’t get any improvement, and that was crushing to me because I had hoped and waited so long.

I just kept praying, waiting, reading and hoping. And then boom, all the sudden I got a phone call from UC Irvine saying they wanted me to participate in their stem cell trial for RP. They said I’d be the third person in the world to have it done and the first in their clinical trial. They told me I was to be the first North American patient to have progenitor cells put in my eye, which is pretty amazing.

Q: Was it easy to decide to participate in the UC Irvine CIRM-funded trial?

Yes. But don’t get me wrong, I’m human. I was a little scared. It’s a new thing and you have to sign papers saying that you understand that we don’t exactly know what the results will be. Essentially, you are agreeing to be a pathfinder.

Luckily, I have not had any adverse effects since the trial. But I’ve always had a great deal of faith in stem cells. For years, I’ve been hearing about it and I’ve always put my hopes in stem cells thinking that that’s going to be the answer for blindness.

Q: Have you seen any improvements in your sight since participating in this trial?

I was treated a year ago in June. The stem cell transplant was in my left eye, my worse eye that has never gotten better. It’s been about 15 months now, and I started to see improvement after about two months following the treatment. When I would go into my bathroom, I noticed that it was a lot brighter. I didn’t know if I was imagining things, but I called a friend and said, “I don’t know if I’m imagining things but I’m getting more light perception in this eye.”

Sure enough, over a period of about eight months, I had gradual improvement in light perception. Then I leveled off, but now there is no question that I’m photo sensitive. When I go out, I use my sunglasses, and I see a whole lot more light.

Because I was one of the first patients in the trial, they had to give me a small dose of cells to test for safety. So it was amazing that a smaller dose of cells was still able to help me gain back some sight! One of the improvements that I’ve had is that I can actually see the image of my finger waving back and forth on my left side, which I couldn’t before when I put mascara on. I say this because I have put lip pencil all over my mouth by accident. That must have been a real sight! For a woman, putting on makeup is really important.

Q: What was your experience like participating in the UC Irvine trial?

Dr. Klassen who runs the UC Irvine stem cell trial for RP is an amazing person. He was in the room with me during the transplant procedure. I have such a high regard and respect for Dr. Klassen because he’s been working on the cure for RP as long as I’ve had it. He’s someone who’s dedicated his life to trying to find an answer to a disease that I’ve been dealing with on a day-to-day basis.

Dr. Klassen had the opportunity to become a retinal surgeon and make much more money in a different area. But because it was too crushing to talk to patients and give them such a sad diagnosis, he decided he was going to do something about it. When I heard that, I just never forgot it. He’s a wonderful man and he’s really dedicated to this cause.

Q: How have you been an advocate for RP and blindness?

I’ve been an advocate for the visually impaired in many different aspects. I have raised money for different research foundations and donated my time as a host and an MC to various charities through radio shows. I’ve had a voice in the visually impaired community in one way or another on and off for 15 years.

I also started getting involved in Americans for Cures only a few months ago. I am helping them raise awareness about Proposition 71, which created CIRM, and the importance of funding stem cell research in the future.

I may in this lifetime get actual vision again, a real second vision. But in the meantime, I’ve been working on my higher self, which is good because a friend of mine who is totally blind reminded me today, “Kristin, just remember, don’t live for tomorrow just getting that eye sight back”. My friend was born blind. I told him he is absolutely right. I know I can lead a joyful life either way. But trust me, having a cure for RP would be the icing on the cake for me.

Q: Why is it important to be a patient advocate?

I think it’s so important from a number of different aspects, and I really felt this at the International Society for Stem Cell Research (ISSCR) conference in San Francisco this summer when certain people came to talk to me afterwards, especially researchers and scientists. They don’t get to see the perspective of the patient because they are on the other side of the fence.

I think it’s very important to be a patient advocate because when you have a personal story, it resonates with people much more than just reading about something or hearing about something on a ballot.  It’s really vital for the future. Everybody has somebody or knows somebody who had macular degeneration or became visually impaired. If they don’t, they need to be educated about it.

Q: Tell us about your Radio Show.

My radio show “Second Vision” is about personal development and reinventing yourself and your life’s vision when the first one fails. It was the first internet radio show to support the blind and visually impaired, so that’s why I’m passionate about it. I’ve had scores of authors on there over the years who’ve written amazing books about how to better yourself and personal stories from people who have overcome adversity from all different types of challenges in terms of emotional health, physical health or problems in their lives. You can find anything on the Second Vision website from interviews on Reiki and meditation to Erik Weihenmayer, the blind man who climbed the seven summits (the highest mountains of each of the seven continents).

Q: Why is stem cell research important?

I do think that stem cells will help people with blindness. I don’t know whether it will be a 100% treatment. Scientists may have to do something else along the way to perfect stem cell treatments whether it’s gene therapy or changing the number of cells or types of cells they inject into the eye. I really do have a huge amount of faith in stem cells. If they can regenerate other parts of the body, I think the eye will be no different.

To read more about Kristin Macdonald and her quest for a Second Vision, please visit her website.


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Trash talking and creating a stem cell community

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Imilce Rodriguez-Fernandez likes to talk trash. No, really, she does. In her case it’s cellular trash, the kind that builds up in our cells and has to be removed to ensure the cells don’t become sick.

Imilce was one of several stem cell researchers who took part in a couple of public events over the weekend, on either side of San Francisco Bay, that served to span both a geographical and generational divide and create a common sense of community.

The first event was at the Buck Institute for Research on Aging in Marin County, near San Francisco. It was titled “Stem Cell Celebration” and that’s pretty much what it was. It featured some extraordinary young scientists from the Buck talking about the work they are doing in uncovering some of the connections between aging and chronic diseases, and coming up with solutions to stop or even reverse some of those changes.

One of those scientists was Imilce. She explained that just as it is important for people to get rid of their trash so they can have a clean, healthy home, so it is important for our cells to do the same. Cells that fail to get rid of their protein trash become sick, unhealthy and ultimately stop working.

Imilce is exploring the cellular janitorial services our bodies have developed to deal with trash, and trying to find ways to enhance them so they are more effective, particularly as we age and those janitorial services aren’t as efficient as they were in our youth.

Unlocking the secrets of premature aging

Chris Wiley, another postdoctoral researcher at the Buck, showed that some medications that are used to treat HIV may be life-saving on one level, preventing the onset of full-blown AIDS, but that those benefits come with a cost, namely premature aging. Chris said the impact of aging doesn’t just affect one cell or one part of the body, but ripples out affecting other cells and other parts of the body. By studying the impact those medications have on our bodies he’s hoping to find ways to maintain the benefits of those drugs, but get rid of the downside.

Creating a Community

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Across the Bay, the U.C. Berkeley Student Society for Stem Cell Research held it’s 4th annual conference and the theme was “Culturing a Stem Cell Community.”

The list of speakers was a Who’s Who of CIRM-funded scientists from U.C. Davis’ Jan Nolta and Paul Knoepfler, to U.C. Irvine’s Henry Klassen and U.C. Berkeley’s David Schaffer. The talks ranged from progress in fighting blindness, to how advances in stem cell gene editing are cause for celebration, and concern.

What struck me most about both meetings was the age divide. At the Buck those presenting were young scientists, millennials; the audience was considerably older, baby boomers. At UC Berkeley it was the reverse; the presenters were experienced scientists of the baby boom generation, and the audience were keen young students representing the next generation of scientists.

Bridging the divide

But regardless of the age differences there was a shared sense of involvement, a feeling that regardless of which side of the audience we are on we all have something in common, we are all part of the stem cell community.

All communities have a story, something that helps bind them together and gives them a sense of common purpose. For the stem cell community there is not one single story, there are many. But while those stories all start from a different place, they end up with a common theme; inspiration, determination and hope.

 

Seeing is believing: how some scientists – including two funded by CIRM – are working to help the blind see

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How retinitis pigmentosa destroys vision – new stem cell research may help reverse that

“A pale hue”. For most of us that is a simple description, an observation about color. For Kristin Macdonald it’s a glimpse of the future. In some ways it’s a miracle. Kristin lost her sight to retinitis pigmentosa (RP). For many years she was virtually blind. But now, thanks to a clinical trial funded by CIRM she is starting to see again.

Kristin’s story is one of several examples of restoring sight in an article entitled “Why There’s New Hope About Ending Blindness” in the latest issue of National Geographic.  The article explores different approaches to treating people who were either born without vision or lost their vision due to disease or injury.

Two of those stories feature research that CIRM has funded. One is the work that is helping Kristin. Retinitis pigmentosa is a relatively rare condition that destroys the photoreceptors at the back of the eye, the cells that actually allow us to sense light. The National Geographic piece highlights how a research team at the University of California, Irvine, led by Dr. Henry Klassen, has been working on a way to use stem cells to replace and repair the cells damaged by RP.

“Klassen has spent 30 years studying how to coax progenitor cells—former stem cells that have begun to move toward being specific cell types—into replacing or rehabilitating failed retinal cells. Having successfully used retinal progenitor cells to improve vision in mice, rats, cats, dogs, and pigs, he’s testing a similar treatment in people with advanced retinitis pigmentosa.”

We recently blogged about this work and the fact that this team just passed it’s first major milestone – – showing that in the first nine patients treated none experienced any serious side effects. A Phase 1 clinical trial like this is designed to test for safety, so it usually involves the use of relatively small numbers of cells. The fact that some of those treated, like Kristin, are showing signs of improvement in their vision is quite encouraging. We will be following this work very closely and reporting new results as soon as they are available.

The other CIRM-supported research featured in the article is led by what the writer calls “an eyeball dream team” featuring University of Southern California’s Dr. Mark Humayun, described as “a courteous, efficient, impeccably besuited man.” And it’s true, he is.

The team is developing a stem cell device to help treat age-related macular degeneration, the leading cause of vision loss in the US.

“He and his fellow principal investigator, University of California, Santa Barbara stem cell biologist Dennis Clegg, call it simply a patch. That patch’s chassis, made of the same stuff used to coat wiring for pacemakers and neural implants, is wafer thin, bottle shaped, and the size of a fat grain of rice. Onto this speck Clegg distributes 120,000 cells derived from embryonic stem cells.”

Humayun and Clegg have just started their clinical trial with this work so it is likely going to be some time before we have any results.

These are just two of the many different approaches, using several different methods, to address vision loss. The article is a fascinating read, giving you a sense of how science is transforming people’s lives. It’s also wonderfully written by David Dobbs, including observations like this:

“Neuroscientists love the eye because “it’s the only place you see the brain without drilling a hole,” as one put it to me.”

For a vision of the future, a future that could mean restoring vision to those who have lost it, it’s a terrific read.

 

CIRM-funded stem cell clinical trial for retinitis pigmentosa focuses on next stage

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How retinitis pigmentosa erodes normal vision

The failure rate for clinical trials is depressingly high. A study from Tufts University in 2010  found that for small molecules – the substances that make up more than 90 percent of the drugs on the market today – the odds of getting from a Phase 1 trial to approval by the Food and Drug Administration are just 13 percent. For stem cell therapies the odds are even lower.

That’s why, whenever a stem cell therapy shows good results it’s an encouraging sign, particularly when that therapy is one that we at CIRM are funding. So we were more than a little happy to hear that Dr. Henry Klassen and his team at jCyte and the University of California, Irvine have apparently cleared the first hurdle with their treatment for retinitis pigmentosa (RP).

jCyte has announced that the first nine patients treated for RP have shown no serious side effects, and they are now planning the next phase of their Phase 1/2a safety trial.

In a news release Klassen, the co-founder of jCyte, said:

“We are pleased with the results. Retinitis pigmentosa is an incurable retinal disease that first impacts people’s night vision and then progressively robs them of sight altogether. This is an important milestone in our effort to treat these patients.”

The therapy involves injecting human retinal progenitor cells into one eye to help save the light sensing cells that are destroyed by the disease. This enables the researchers to compare the treated eye with the untreated eye to see if there are any changes or improvements in vision.

So far, the trial has undergone four separate reviews by the Data Safety Monitoring Board (DSMB), an independent group of experts that examines data from trials to ensure they meet all safety standards and that results show patients are not in jeopardy. Results from the first nine people treated are encouraging.

The approach this RP trial is taking has a couple of advantages. Often when transplanting organs or cells from one person into another, the recipient has to undergo some kind of immunosuppression, to stop their body rejecting the transplant. But earlier studies show that transplanting these kinds of progenitor cells into the eye doesn’t appear to cause any immunological response. That means patients in the study don’t have to undergo any immunosuppression. Because of that, the procedure is relatively simple to perform and can be done in a doctor’s office rather than a hospital. For the estimated 1.5 million people worldwide who have RP that could make getting treatment relatively easy.

Of course the big question now is not only was it safe – it appears to be – but does it work? Did any of those people treated experience improvements in their vision? We will share those results with you as soon as the researchers make them available.

Next step for the clinical trial is to recruit more patients, and treat them with a higher number of cells. There’s still a long way to go before we will know if this treatment works, if it either slows down, stops, or better still helps reverse some of the effects of RP. But this is a really encouraging first step.


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On the Hunt for Huntington’s Disease Treatments in the New Millennium

“Over the next five to ten years, we want to make Huntington’s disease an increasingly treatable condition.”

This bold and inspiring statement was made by Dr. Ray Dorsey at the inaugural HD-CARE symposium for Huntington’s disease (HD) research held at UC Irvine last month. The event brought together scientists, doctors, patients, family members, and caregivers to discuss the latest discoveries in HD research and to talk openly about how we can address the unmet needs of patients suffering from this terrible, deadly neurodegenerative disease.

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Symposium speakers and HD-CARE Board Members

The symposium was hosted by HD-CARE, a non-profit organization established three years ago to support HD research and patient care. Frances Saldaña, HD-CARE president and a CIRM patient advocate, established this symposium with the goal of bringing new hope to HD patients and their family members.

Frances Saldana, HD-CARE President & Patient Advocate

Frances Saldana

“There is so much exciting research taking place all over the world that one can hardly contain oneself with excitement and hope,” explained Saldaña. “It is only right to share this scientific information and breakthroughs in HD research that has undoubtedly given our families so much hope.”

Recent breakthroughs

The symposium featured talks by scientists and doctors that spanned a broad range of topics including the recent progress of using human stem cells to model HD, the hope and hype of gene editing, and the benefits of in vitro fertilization (IVF) for HD families.

Dr. Ray Dorsey, Professor at the University of Rochester Medical Center, gave the keynote address. Inspiring from the start, he captured the audience’s attention by posing the question, “Why are we here?” To which he answered, “I think we are here to change this sign, which says Huntington’s disease is a fatal genetic neurodegenerative disease, to one that says HD is an increasingly treatable condition. Over the next five to ten years, we want to make HD an increasingly treatable condition.”

Referencing the HIV epidemic in the 1980s, Dorsey pointed out that there is precedent. What was thought to be a disease with a rapid death sentence is now, decades later, a treatable condition, and his belief is that the same can be done for HD patients in the near future.

Dorsey next highlighted major clinical advances in HD treatment including a record ten drugs currently in development in 2016. Treatments that he felt had particular promise included a gene silencing therapy by Ionis Pharmaceuticals, which is the first treatment being tested in clinical trials that targets the cause of HD. Dorsey also mentioned two drugs, Pridopidine and SD-809 (a modified version of the FDA-approved drug Tetrabenazine), that are used to treat symptoms of HD.

My favorite part of the talk was the end where he described his latest efforts to develop digital biomarkers that use smart phones and wearables to monitor a patient’s response to HD treatments in their own home.  This technology will not only make it easier to determine which treatments are effective for HD, but will also improve the quality of care patients receive during clinical trials.

Dr. Ray Dorsey

Dr. Ray Dorsey

“We think that these devices, which allow us to make assessments of how people are doing with a given condition, will soon be able to connect patients to clinicians so they can receive care regardless of who they are or where they live. We hope that for Huntington’s disease, these tools and technologies will enable us to connect patients to effective treatments for HD.”

Battle cry for change

While the science at the symposium was certainly encouraging, the voices of the patients and patient advocates made the strongest impression. Many of them spoke out to share their stories or ask questions. Others, like Saldaña, advocated for faster progress towards a cure.

“This disease is one in which family members and friends need to rally together and demand that research be properly funded to end this generational disease.  It is not one in which policy makers can sit around and wonder if they should fund it…it is a five-alarm fire that needs immediate action, and from the families, a fierce battle cry asking from policy makers and decision makers to fund aggressive research to end Huntington’s disease.”

Julie Rosling, Frances Saldana,

Julie Rosling receives the Patient Advocacy Award from HD-CARE’s Frances Saldana and Karen Thornburn

A particularly moving event was the presentation of the 2016 Patient Advocacy Award to Julie Rosling. Members of the HD-CARE board presented Rosling with a trophy to honor her brave efforts in advocating for HD patient rights. Saldaña described how Rosling was fearless at a HD patient-focused drug development meeting with the FDA in DC last fall. Along with other patients, she stood up and challenged the FDA to move HD into the fast track category for approving clinical trials.

A similar demand for regulatory change was brought up during the symposium regarding the approval of stem cell treatments for HD. As the representative for CIRM, I had a few moments to talk about our new Stem Cell Champions campaign, which is actively recruiting patient advocates that can work with us to help make the FDA approval process for stem cell treatments faster and more efficient. Our colleagues at Americans for Cures also spoke briefly about their efforts to promote the acceleration of stem cell treatments and improve the lives of HD patients.

By the end of the symposium, there was an overwhelming feeling of accomplishment and more importantly a renewed sense of hope for the future of HD treatments.

“It was extremely successful and I believe everyone left feeling very optimistic about the future for HD families,” said Saldaña. “There is a light at the end of the tunnel.”

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Patient Advocates Ron Shapiro, Adrienne Shapiro, David Saldana, Frances Saldana, Daniel Medina with Karen Ring from CIRM


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