A stem cell clinical trial for blindness: watch Rosie’s story

Everything we do at CIRM is laser-focused on our mission: to accelerate stem cell treatments for patients with unmet medical needs. So, you might imagine what a thrill it is to meet the people who could be helped by the stem cell research we fund. People like Rosie Barrero who suffers from Retinitis Pigmentosa (RP), an inherited, incurable form of blindness, which she describes as “an impressionist painting in a foggy room”.

The CIRM team first met Rosie Barrero back in 2012 at one of our governing Board meetings. She and her husband, German, attended the meeting to advocate for a research grant application submitted by UC Irvine’s Henry Klassen. The research project aimed to bring a stem cell-based therapy for RP to clinical trials. The Board approved the project giving a glimmer of hope to Rosie and many others stricken with RP.

Now, that hope has become a reality in the form of a Food and Drug Administration (FDA)-approved clinical trial which Rosie participated in last year. Sponsored by jCyte, a company Klassen founded, the CIRM-funded trial is testing the safety and effectiveness of a non-surgical treatment for RP that involves injecting stem cells into the eye to help save or even restore the light-sensing cells in the back of the eye. The small trial has shown no negative side effects and a larger, follow-up trial, also funded by CIRM, is now recruiting patients.

Almost five years after her first visit, Rosie returned to the governing Board in February and sprinkled in some of her witty humor to describe her preliminary yet encouraging results.

“It has made a difference. I’m still afraid of public speaking but early on [before the clinical trial] it was much easier because I couldn’t see any of you. But, hello everybody! I can see you guys. I can see this room. I can see a lot of things.”

After the meeting, she sat down for an interview with the Stem Cellar team to talk about her RP story and her experience as a clinical trial participant. The three-minute video above is based on that interview. Watch it and be inspired!

Stem cells reveal developmental defects in Huntington’s disease

Three letters, C-A-G, can make the difference between being healthy and having a genetic brain disorder called Huntington’s disease (HD). HD is a progressive neurodegenerative disease that affects movement, cognition and personality. Currently more than 30,000 Americans have HD and there is no cure or treatment to stop the disease from progressing.

A genetic mutation in the huntingtin gene. caused by an expanded repeat of CAG nucleotides, the building blocks of DNA that make our genes, is responsible for causing HD. Normal people have less than 26 CAG repeats while those with 40 or more repeats will get HD. The reasons are still unknown why this trinucleotide expansion causes the disease, but scientists hypothesize that the extra CAG copies in the huntingtin gene produce a mutant version of the Huntingtin protein, one that doesn’t function the way the normal protein should.

The HD mutation causes neurodegeneration.

As with many diseases, things start to go wrong in the body long before symptoms of the disease reveal themselves. This is the case for HD, where symptoms typically manifest in patients between the ages of 30 and 50 but problems at the molecular and cellular level occur decades before. Because of this, scientists are generating new models of HD to unravel the mechanisms that cause this disease early on in development.

Induced pluripotent stem cells (iPSCs) derived from HD patients with expanded CAG repeats are an example of a cell-based model that scientists are using to understand how HD affects brain development. In a CIRM-funded study published today in the journal Nature Neuroscience, scientists from the HD iPSC Consortium used HD iPSCs to study how the HD mutation causes problems with neurodevelopment.

They analyzed neural cells made from HD patient iPSCs and looked at what genes displayed abnormal activity compared to healthy neural cells. Using a technique called RNA-seq analysis, they found that many of these “altered” genes in HD cells played important roles in the development and maturation of neurons, the nerve cells in the brain. They also observed differences in the structure of HD neurons compared to healthy neurons when grown in a lab. These findings suggest that HD patients likely have problems with neurodevelopment and adult neurogenesis, the process where the adult stem cells in your brain generate new neurons and other brain cells.

After pinpointing the gene networks that were altered in HD neurons, they identified a small molecule drug called isoxazole-9 (Isx-9) that specifically targets these networks and rescues some of the HD-related symptoms they observed in these neurons. They also tested Isx-9 in a mouse model of HD and found that the drug improved their cognition and other symptoms related to impaired neurogenesis.

The authors conclude from their findings that the HD mutation disrupts gene networks that affect neurodevelopment and neurogenesis. These networks can be targeted by Isx-9, which rescues HD symptoms and improves the mental capacity of HD mice, suggesting that future treatments for HD should focus on targeting these early stage events.

I reached out to the leading authors of this study to gain more insights into their work. Below is a short interview with Dr. Leslie Thompson from UC Irvine, Dr. Clive Svendsen from Cedars-Sinai, and Dr. Steven Finkbeiner from the Gladstone Institutes. The responses were mutually contributed.

Leslie Thompson

Steven Finkbeiner

Clive Svendsen

 

 

 

 

 

 Q: What is the mission of the HD iPSC Consortium?

To create a resource for the HD community of HD derived stem cell lines as well as tackling problems that would be difficult to do by any lab on its own.  Through the diverse expertise represented by the consortium members, we have been able to carry out deep and broad analyses of HD-associated phenotypes [observable characteristics derived from your genome].  The authorship of the paper  – the HD iPSC consortium (and of the previous consortium paper in 2012) – reflects this goal of enabling a consortium and giving recognition to the individuals who are part of it.

Q: What is the significance of the findings in your study and what novel insights does it bring to the HD field?

 Our data revealed a surprising neurodevelopmental effect of highly expanded repeats on the HD neural cells.  A third of the changes reflected changes in networks that regulate development and maturation of neurons and when compared to neurodevelopment pathways in mice, showed that maturation appeared to be impacted.  We think that the significance is that there may be very early changes in HD brain that may contribute to later vulnerability of the brain due to the HD mutation.  This is compounded by the inability to mount normal adult neurogenesis or formation of new neurons which could compensate for the effects of mutant HTT.  The genetic mutation is present from birth and with differentiated iPSCs, we are picking up signals earlier than we expected that may reflect alterations that create increased susceptibility or limited homeostatic reserves, so with the passage of time, symptoms do result.

What we find encouraging is that using a small molecule that targets the pathways that came out of the analysis, we protected against the impact of the HD mutation, even after differentiation of the cells or in an adult mouse that had had the mutation present throughout its development.

Q: There’s a lot of evidence suggesting defects in neurodevelopment and neurogenesis cause HD. How does your study add to this idea?

Agree completely that there are a number of cell, mouse and human studies that suggest that there are problems with neurodevelopment and neurogenesis in HD.  Our study adds to this by defining some of the specific networks that may be regulating these effects so that drugs can be developed around them.  Isx9, which was used to target these pathways specifically, shows that even with these early changes, one can potentially alleviate the effects. In many of the assays, the cells were already through the early neurodevelopmental stages and therefore would have the deficits present.  But they could still be rescued.

Q: Has Isx-9 been used previously in cell or animal models of HD or other neurodegenerative diseases? Could it help HD patients who already are symptomatic?

The compound has not been used that we know of in animal models to treat neurodegeneration, although was shown to affect neurogenesis and memory in mice. Isx9 was used in a study by Stuart Lipton in Parkinson’s iPSC-derived neurons in one study and it had a protective effect on apoptosis [cell death] in a study by Ryan SD et al., 2013, Cell.

We think this type of compound could help patients who are symptomatic.  Isx-9 itself is a fairly pleiotropic drug [having multiple effects] and more research would be needed [to test its safety and efficacy].

Q: Have you treated HD mice with Isx-9 during early development to see whether the molecule improves HD symptoms?

Not yet, but we would like to.

Q: What are your next steps following this study and do you have plans to translate this research into humans?

We are following up on the research in more mature HD neurons and to determine at what stages one can rescue the HD phenotypes in mice.  Also, we would need to do pharmacodynamics and other types of assays in preclinical models to assess efficacy and then could envision going into human trials with a better characterized drug.  Our goal is to ultimately translate this to human treatments in general and specifically by targeting these altered pathways.

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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Cured by Stem Cells

cirm-2016-annual-report-web-12

To get anywhere you need a good map, and you need to check it constantly to make sure you are still on the right path and haven’t strayed off course. A year ago the CIRM Board gave us a map, a Strategic Plan, that laid out our course for the next five years. Our Annual Report for 2016, now online, is our way of checking that we are still on the right path.

I think, without wishing to boast, that it’s safe to say not only are we on target, but we might even be a little bit ahead of schedule.

The Annual Report is chock full of facts and figures but at the heart of it are the stories of the people who are the focus of all that we do, the patients. We profile six patients and one patient advocate, each of whom has an extraordinary story to tell, and each of whom exemplifies the importance of the work we support.

brenden_stories_of_hope

Brenden Whittaker: Cured

Two stand out for one simple reason, they were both cured of life-threatening conditions. Now, cured is not a word we use lightly. The stem cell field has been rife with hyperbole over the years so we are always very cautious in the way we talk about the impact of treatments. But in these two cases there is no need to hold back: Evangelina Padilla Vaccaro and Brenden Whittaker have been cured.

evangelina

Evangelina: Cured

 

In the coming weeks we’ll feature our conversations with all those profiled in the Annual Report, giving you a better idea of the impact the stem cell treatments have had on their lives and the lives of their family. But today we just wanted to give a broad overview of the Annual Report.

The Strategic Plan was very specific in the goals it laid out for us. As an agency we had six big goals, but each Team within the agency, and each individual within those teams had their own goals. They were our own mini-maps if you like, to help us keep track of where we were individually, knowing that every time an individual met a goal they helped the Team get closer to meeting its goals.

As you read through the report you’ll see we did a pretty good job of meeting our targets. In fact, we missed only one and we’re hoping to make up for that early in 2017.

But good as 2016 was, we know that to truly fulfill our mission of accelerating treatments to patients with unmet medical needs we are going to have do equally well, if not even better, in 2017.

That work starts today.

 

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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CIRM-funded stem cell trial for retinitis pigmentosa makes progress

A CIRM-funded clinical trial for retinitis pigmentosa (RP), a degenerative eye disease that causes blindness, recently reached its next milestone and announced the completion of its patient enrollment for a phase I/IIa study testing a stem cell derived therapy. This is a major step forward in determining whether this approach is both safe and effective at improving sight in RP patients.

retinitis pigmentosas_1RP is a genetically inherited disease that destroys the light-sensing photoreceptor cells at the back of the eye. Symptoms of the disease typically appear in childhood and often cause blindness by the age of 40. RP affects approximately 100,000 people in the US, and there are no effective treatments.

Stem cell treatment for RP

Regenerative medicine offers a promising strategy for treating RP by replacing the lost or damaged photoreceptors in the retina with healthy retinal cells derived from human stem cells.

CIRM is funding a clinical trial that’s testing a stem cell-based treatment for advanced RP. The trial is sponsored by a California-based company called jCyte, which was founded in 2012 by Dr. Henry Klassen and Dr. Jing Yang, both currently professors at UC Irvine.

The treatment involves injecting human retinal progenitor cells, which are derived from adult stem cells, into the damaged area of the retina at the back of the eye to hopefully improve vision. These progenitor cells could either replace the damaged photoreceptors in the eye, or could help rescue the remaining photoreceptors from being destroyed.

RP clinical trials makes progress

Earlier this year, jCyte reported that they had treated the first nine patients in their phase I/IIa safety trial and did not observe any negative side effects caused by the treatment. Today, they announced that they have finished the trial enrollment with a total of 28 patients. Four different doses of retinal progenitor cells were tested in this patient group to determine both safety and the optimal dose of cells. While the results of this trial won’t be available until next year, eight of the enrolled patients have already completed the one-year study and have shown promising safety results.

In a jCyte news release, Dr. Klassen explained:

Klassen“We have successfully completed four DSMB (Data Safety Monitoring Board) reviews. So far, trial participants have had no significant side effects, with good tolerance of the injected cells. We are quite gratified by the results.”

CIRM is also happy to hear these positive findings as proving that a stem cell treatment is safe in patients is essential for moving a clinical trial forward. Jonathan Thomas, Chairman of the CIRM Governing Board commented in a CIRM news release:

Jonathan Thomas

Jonathan Thomas

“We are really encouraged by the preliminary safety results of the jCyte trial. RP is a rare disease and an unmet medical need that could benefit from advances in stem cell-based treatments. The jCyte trial will hopefully pave the way for determining how stem cells can improve vision in RP patients, and ultimately other diseases of blindness.”

Next steps

As this trial moves forward, jCyte hopes to begin planning a phase IIb trial that will determine whether their stem cell-based therapy is effective at improving vision in advanced RP patients.

“I look forward to the next stage of development towards commercialization,” said jCyte CEO Paul Bresge. “We never lose sight of our singular goal: to ultimately deliver this much-needed therapy to patients.”

If all goes well, additional RP patients will be needed to participate in the second phase of the jCyte trial. Patients who are interested in learning more about this trial or enrolling in future trials, should visit the jCyte website.

If you want to learn more about how stem cells could potentially yield new treatments for diseases of blindness, watch our video “Eyeing Stem Cell Therapies for Vision Loss”.


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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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