Throwback Thursday: Progress to a Cure for Diseases of Blindness

Welcome back to our “Throwback Thursday” series on the Stem Cellar. Over the years, we’ve accumulated an arsenal of exciting stem cell stories about advances towards stem cell-based cures for serious diseases. This month we’re featuring stories about CIRM-funded clinical trials for blindness.

2017 has been an exciting year for two CIRM-funded clinical trials that are testing stem cell-based therapies for diseases of blindness. A company called Regenerative Patch Technologies (RPT) is transplanting a sheet of embryonic stem cell-derived retinal support cells into patients with the dry form of age-related macular degeneration, a disease that degrades the eye’s macula, the center of the retina that controls central vision. The other trial, sponsored by a company called jCyte, is using human retinal progenitor cells to treat retinitis pigmentosa, a rare genetic disease that destroys the light-sensing cells in the retina, causing tunnel vision and eventually blindness.

 

Both trials are in the early stages, testing the safety of their respective stem cell therapies. But the teams are hopeful that these treatments will stop the progression of or even restore some form of vision in patients. In the past few months, both RPT and jCyte have shared exciting news about the progress of these trials which are detailed below.

Macular Degeneration Trial Gets a New Investor

In April, RPT announced that they have a new funding partner to further develop their stem cell therapy for age-related macular degeneration (AMD). They are partnering with Japan’s Santen Pharmaceutical Company, which specializes in developing ophthalmology or eye therapies.

AMD is the leading cause of blindness in elderly people and is projected to affect almost 200 million people worldwide by 2020. There is no cure or treatment that can restore vision in AMD patients, but stem cell transplants offer a potential therapeutic option.

RPT believes that their newfound partnership with Santen will accelerate the development of their stem cell therapy and ultimately fulfill an unmet medical need. RPT’s co-founder, Dr. Dennis Clegg, commented in a CIRM news release, “the ability to partner with a global leader in ophthalmology like Santen is very exciting. Such a strong partnership will greatly accelerate RPT’s ability to develop our product safely and effectively.”

This promising relationship highlights CIRM’s efforts to partner our clinical programs with outside investors to boost their chance of success. It also shows confidence in the future success of RPT’s stem cell-based therapy for AMD.

Retinitis Pigmentosa Trial Advances to Phase 2 and Receives RMAT Status

In May, the US Food and Drug Administration (FDA) approved jCyte’s RP trial for Regenerative Medicine Advanced Therapy (RMAT) status, which could pave the way for accelerated approval of this stem cell therapy for patients with RP.

RMAT is a new status established under the 21st Century Cures Act – a law enacted by Congress in December of 2016 to address the need for a more efficient regulatory approval process for stem cell therapies that can treat serious or life-threatening diseases. Trial sponsors of RMAT designated therapies can meet with the FDA earlier in the trial process and are eligible for priority review and accelerated approval.

jCyte’s RMAT status is well deserved. Their Phase 1 trial was successful, proving the treatment was safe and well-tolerated in patients. More importantly, some of the patients revealed that their sight has improved following their stem cell transplant. We’ve shared the inspiring stories of two patients, Rosie Barrero and Kristin Macdonald, previously on the Stem Cellar.

Rosie Barrero

Kristin MacDonald

Both Rosie and Kristin were enrolled in the Phase 1 trial and received an injection of retinal progenitor cells in a single eye. Rosie said that she went from complete darkness to being able to see shapes, colors, and the faces of her family and friends. Kristin was the first patient treated in jCyte’s trial, and she said she is now more sensitive to light and can see shapes well enough to put on her own makeup.

Encouraged by these positive results, jCyte launched its Phase 2 trial in April with funding from CIRM. They will test the same stem cell therapy in a larger group of 70 patients and monitor their progress over the next year.

Progress to a Cure for Blindness

We know very well that scientific progress takes time, and unfortunately we don’t know when there will be a cure for blindness. However, with the advances that these two CIRM-funded trials have made in the past year, our confidence that these stem cell treatments will one day benefit patients with RP and AMD is growing.

I’ll leave you with an inspiring video of Rosie Barrero about her experience with RP and how participating in jCytes trial has changed her life. Her story is an important reminder of why CIRM exists and why supporting stem cell research in particular, and research in general, is vital for the future health of patients.


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

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

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

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

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

Jennifer Malin, United Healthcare

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

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

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

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

Sunil Kadim, QuintilesIMS

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

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

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

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

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

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

Kristin Macdonald

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

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

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

retinitis pigmentosas_1

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.