Stem cell stories that caught our eye: 3 blind mice no more and a tale of two tails

Stem cell image of the week: The demise of Three Blind Mice nursery rhyme (Todd Dubnicoff)
Our stem cell image of the week may mark the beginning of the end of the Three Blind Mice nursery rhyme and, more importantly, usher in a new treatment strategy for people suffering from vision loss. That’s because researchers from Icahn School of Medicine at Mount Sinai, New York report in Nature the ability to reprogram support cells in the eyes of blind mice to become photoreceptors, the light-sensing cells that enable sight. The image is an artistic rendering of the study results by team led Dr. Bo Chen, PhD.

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An artist’s rendering incorporates the images of the Müller glia-derived rod photoreceptors. Image credit: Bo Chen, Ph.D.

The initial inspiration for this project came from an observation in zebrafish. These creatures have the remarkable ability to restore vision after severe eye injuries. It turns out that, in response to injury, a type of cell in the eye called Muller glia – which helps maintain the structure and function of the zebrafish retina – transforms into rod photoreceptors, which allow vision in low light.

Now, Muller glia are found in humans and mice too, so the research team sought to harness this shape-shifting, sight-restoring ability of the Muller glia but in the absence of injury. They first injected a gene into the eyes of mice born blind that stimulated the glia cells to divide and grow. Then, to mimic the reprogramming process seen in zebrafish, specific factors were injected to cause the glia to change identity into photoreceptors.

The researchers showed that the glia-derived photoreceptors functioned just like those observed in normal mice and made the right connections with nerve cells responsible for sending visual information to the brain. The team’s next steps are to not only show the cells are functioning properly in the eye and brain but to also do behavioral studies to confirm that the mice can do tasks that require vision.

If these studies pan out, it could lead to a new therapeutic strategy for blinding diseases like retinitis pigmentosa and macular degeneration. Rather than transplanting replacement cells, this treatment approach would spur our own eyes to repair themselves. In the meantime, CIRM-funded researchers have studies currently in clinical trials testing stem cell-based treatments for retinitis pigmentosa and macular degeneration.

A tale of two tails: one regenerates, the other, not quite so much (Kevin McCormack) One of the wonders of nature, well two if you want to be specific, is how both salamanders and lizards are able to regrow their tails if they lose them. But there is a difference. While salamanders can regrow a tail that is almost identical to the original, lizard’s replacements are rather less impressive. Now researchers have found out why.

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In these fluorescence microscopy images, cross sections of original lizard and salamander tails (left) show cartilage (green) and nerve cells (red). In the regenerated tails (right), the lizard’s is made up mostly of cartilage, while the salamander also has developed new nerve cells. Image: Thomas Lozito

The study, published in the Proceedings of the National Academy of Sciences, shows how a lizard’s new tail doesn’t have bone but instead has cartilage, and also lacks nerve cells. The key apparently is the stem cells both use to regenerate the tail. Salamanders use neural stem cells from their spinal cord and turn them into other types of nervous system cell, such as neurons. Lizards neural stem cells are not able to do this.

The researchers, from the University of Pittsburgh, tested their findings by placing neural stem cells from the axolotl salamander into tail stumps from geckos. They noted that, as those tails regrew, some of those transplanted cells turned into neurons.

In an interview in Science News, study co-author Thomas Lozito says the team hope to take those findings and, using the CRISPR/Cas9 gene-editing tool, see if they can regenerate body parts in other animals:

 “My goal is to make the first mouse that can regenerate its tail. We’re kind of using lizards as a stepping-stone.”

Stem Cell Patch Restores Vision in Patients with Age-Related Macular Degeneration

Stem cell-derived retinal pigmented epithelial cells. Cell borders are green and nuclei are red. (Photo Credit: Dennis Clegg, UCSB Center for Stem Cell Biology and Engineering)

Two UK patients suffering from vision loss caused by age-related macular degeneration (AMD) have regained their sight thanks to a stem cell-based retinal patch developed by researchers from UC Santa Barbara (UCSB). The preliminary results of this promising Phase 1 clinical study were published yesterday in the journal Nature Biotechnology.

AMD is one of the leading causes of blindness and affects over six million people around the world. The disease causes the blurring or complete loss of central vision because of damage to an area of the retina called the macula. There are different stages (early, intermediate, late) and forms of AMD (wet and dry). The most common form is dry AMD which occurs in 90% of patients and is characterized by a slow progression of the disease.

Patching Up Vision Loss

In the current study, UCSB researchers engineered a retinal patch from human embryonic stem cells. These stem cells were matured into a layer of cells at the back of the eye, called the retinal pigment epithelium (RPE), that are damaged in AMD patients. The RPE layer was placed on a synthetic patch that is implanted under the patient’s retina to replace the damaged cells and hopefully improve the patient’s vision.

The stem cell-based eyepatches are being implanted in patients with severe vision loss caused by the wet form of AMD in a Phase 1 clinical trial at the Moorfields Eye Hospital NHS Foundation Trust in London, England. The trial was initiated by the London Project to Cure Blindness, which was born from a collaboration between UCSB Professor Peter Coffey and Moorsfields retinal surgeon Lyndon da Cruz. Coffey is a CIRM grantee and credited a CIRM Research Leadership award as one of the grants that supported this current study.

The trial treated a total of 10 patients with the engineered patches and reported 12-month data for two of these patients (a woman in her 60s and a man in his 80s) in the Nature Biotech study. All patients were given local immunosuppression to prevent the rejection of the implanted retinal patches. The study reported “three serious adverse events” that required patients to be readmitted to the hospital, but all were successfully treated. 12-months after treatment, the two patients experienced a significant improvement in their vision and went from not being able to read at all to reading 60-80 words per minute using normal reading glasses.

Successfully Restoring Sight

Douglas Waters, the male patient reported on, was diagnosed with wet AMD in July 2015 and received the treatment in his right eye a few months later. He spoke about the remarkable improvement in his vision following the trial in a news release:

“In the months before the operation my sight was really poor, and I couldn’t see anything out of my right eye. I was struggling to see things clearly, even when up-close. After the surgery my eyesight improved to the point where I can now read the newspaper and help my wife out with the gardening. It’s brilliant what the team have done, and I feel so lucky to have been given my sight back.”

This treatment is “the first description of a complete engineered tissue that has been successfully used in this way.” It’s exciting not only that both patients had a dramatic improvement in their vision, but also that the engineered patches were successful at treating an advanced stage of AMD.

The team will continue to monitor the patients in this trial for the next five years to make sure that the treatment is safe and doesn’t cause tumors or other adverse effects. Peter Coffey highlighted the significance of this study and what it means for patients suffering from AMD in a UCSB news release:

Peter Coffey

“This study represents real progress in regenerative medicine and opens the door to new treatment options for people with age-related macular degeneration. We hope this will lead to an affordable ‘off-the-shelf’ therapy that could be made available to NHS patients within the next five years.”

CIRM-Funded Clinical Trials Targeting Brain and Eye Disorders

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

 This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Our Agency has funded a total of 40 trials since its inception. 23 of these trials were funded after the launch of our Strategic Plan in 2016, bringing us close to the half way point of our goal to fund 50 new clinical trials by 2020.

Today we are featuring CIRM-funded trials in our neurological and eye disorders portfolio.  CIRM has funded a total of nine trials targeting these disease areas, and seven of these trials are currently active. Check out the infographic below for a list of our currently active trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

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.”

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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.

 

 

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!

Stories that caught our eye: new target for killing leukemia cancer stem cells and stem cell vesicles halt glaucoma

New stem cell target for acute myeloid leukemia (Karen Ring).  A new treatment for acute myeloid leukemia, a type of blood cancer that turns bone marrow stem cells cancerous, could be in the works in the form of a cancer stem cell destroying antibody.

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Acute Myeloid Leukemia (Credit: Medscape)

Scientists from the NYU Langone Medical Center and the Memorial Sloan Kettering Cancer Center identified a protein called CD99 that appears more abundantly on the surface of abnormal blood cancer stem cells compared to healthy blood stem cells. They developed an antibody that specifically recognizes and kills the CD99 wielding cancer stem cells while leaving the healthy blood stem cells unharmed.

The CD99 antibody was effective at killing human AML stem cells in a dish and in mice that were transplanted with the same type of cancer stem cells. Further studies revealed that the CD99 antibody when attached to the surface of cancer stem cells, sets off a cascade of enzyme activity that causes these cells to die. These findings suggest that cancer stem cells express more CD99 as a protective mechanism against cell death.

In an interview with Genetic Engineering and Biotechnology News, Chris Park, senior author on the Science Translational Medicine study, explained the importance of their work:

“Our findings not only identify a new molecule expressed on stem cells that drive these human malignancies, but we also show that antibodies against this target can directly kill human AML stem cells. While we still have important details to work out, CD99 is likely to be an exploitable therapeutic target for most AML and MDS patients, and we are working urgently to finalize a therapy for human testing.”

While this work is still in the early stages, Dr. Park stressed that his team is actively working to translate their CD99 antibody therapy into clinical trials.

“With the appropriate support, we believe we can rapidly determine the best antibodies for use in patients, produce them at the quality needed to verify our results, and apply for permission to begin clinical trials.”

 

Peculiar stem cell function may help treat blindness (Todd Dubnicoff). Scientists at the National Eye Institute (NEI) have uncovered a novel function that stem cells use to carry out their healing powers and it may lead to therapies for glaucoma, the leading cause of blindness in United States. Reporting this week in Stem Cells Translational Medicine, the researchers show that stem cells send out regenerative signals by shedding tiny vesicles called exosomes. Once thought to be merely a garbage disposal system, exosomes are now recognized as an important means of communication between cells. As they bud off from the cells, the exosomes carry proteins and genetic material that can be absorbed by other cells.

Microscopy image shows exosomes (green) surrounding retinal ganglion cells (orange and yellow). Credit: Ben Mead

Microscopy image shows exosomes (green) surrounding retinal ganglion cells (orange and yellow). Credit: Ben Mead

The researchers at NEI isolated exosomes from bone marrow stem cells and injected them into the eyes of rats with glaucoma symptoms. Without treatment, these animals lose about 90 percent of their retinal ganglion cells, the cells responsible for forming the optic nerve and for sending visual information to the brain. With the exosome treatment, the rats only lost a third of the retinal ganglion cells. The team determined that microRNAs – small genetic molecules that can inhibit gene activity – inside the exosome were responsible for the effect.

Exosomes have some big advantages over stem cells when comes to developing and manufacturing therapies which lead author Ben Mead explains in a press release picked up by Eureka Alert:

“Exosomes can be purified, stored and precisely dosed in ways that stem cells cannot.”

We’ll definitely keep our eyes on this development. If these glaucoma studies continue to look promising it stands to reason that there would be exosome applications in many other diseases.

Cured by Stem Cells

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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.

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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.

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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.

 

Stem cell stories that caught our eye: potential glaucoma therapy, Parkinson’s model, clinical trial list, cancer immune therapy

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

Stem cells may be option in glaucoma.  A few (potentially) blind mice did not run fast enough in an Iowa lab. But lucky for them they did not run into a farmer’s wife wielding a knife. Instead they had their eye sight saved by a team at the University of Iowa that corrected the plumbing in the back of their eyes with stem cells. They had a rodent version of glaucoma, which allows fluid to build up in the eye causing pressure that eventually damages the optic nerve and leads to blindness.

human eye

The fluid buildup results from a breakdown of the trabecular meshwork, a patch of cells that drains fluid from the eye. The Iowa researchers repaired that highly valuable patch with cells grown from iPS type stem cells created by reprogramming adult cells into an embryonic-like state. The trick with any early stage stem cell is getting it to mature into the desired tissue. This team pulled that off by growing the cells in a culture dish that had previously housed trabecular meshwork cells, which must have left behind some chemical signals that directed the growth of the stem cells.

The cells restored proper drainage in the mice. Also notable, the cells not only acted to replace damaged tissue directly, but they also seem to have summoned the eye’s own healing powers to do more repair. The research team also worked at the university affiliated Veterans Affairs Hospital, and the VA system issued a press release on the work published in the Proceedings of the National Academy of sciences, which was posted by Science Codex.

 

A “mini-brain” from a key area.   The brain is far from a uniform organ. Its many distinct divisions have very different functions. A few research teams have succeeded in coaxing stem cells into forming multi-layered clumps of cells referred to as “brain organoids” that mimic some brain activity, but those have generally been parts of the brain near the surface responsible for speech, learning and memory. Now a team in Singapore has created an organoid that shows activity of the mid-brain, that deep central highway for signals key to vision, hearing and movement.

The midbrain houses the dopamine nerves damaged or lost in Parkinson’s disease, so the mini-brains in lab dishes become immediate candidates for studying potential therapies and they are likely to provide more accurate results than current animal models.

 “Considering one of the biggest challenges we face in PD research is the lack of accessibility to the human brains, we have achieved a significant step forward. The midbrain organoids display great potential in replacing animals’ brains which are currently used in research,” said Ng Huck Hui of A*Star’s Genome Institute of Singapore where the research was conducted in a press release posted by Nanowerk.

The website Mashable had a reporter at the press conference in Singapore when the institute announce the publication of the research in Cell Stem Cell. They have some nice photos of the organoids as well as a microscopic image showing the cells containing a black pigment typical of midbrain cells, one of the bits of proof the team needed to show they created what they wanted.

 

Stem cell clinical trials listings.  Not a day goes by that I, or one of my colleagues, do not refer a desperate patient or family member—often several per day—to the web site clinicaltrials.gov. We do it with a bit of unease and usually some caveats but it is the only resource out there providing any kind of searchable listing of clinical trials. Not everything listed at this site maintained by the National Institutes of Health (NIH) is a great clinical trial. NIH maintains the site, and sets certain baseline criteria to be listed, but the agency does not vet postings.

Over the past year a new controversy has cropped up at the site. A number of for profit clinics have registered trials that require patients to pay many thousands of dollars for the experimental stem cell procedure.  Generally, in clinical trials, participation is free for patients. Kaiser Health News, an independent news wire supported by the Kaiser Family Foundation distributed a story this week on the phenomenon that was picked up by a few outlets including the Washington Post. But the version with the best links to added information ran in Stat, an online health industry portal developed by The Boston Globe, which has become one of my favorite morning reads.

The story leads with an anecdote about Linda Smith who went to the trials site to look for stem cell therapies for her arthritic knees. She found a listing from StemGenex and called the listed contact only to find out she would first have to pay $14,000 for the experimental treatment. The company told the author that they are not charging for participation in the posted clinical trial because it only covers the observation phase after the therapy, not the procedure itself. The reporter found multiple critics who suggested the company was splitting hairs a bit too finely with that explanation.

But the NIH came in for just as much criticism for allowing those trials to be listed at all. The web site already requires organizations listing trials to disclose information about the committees that oversee the safety of the patients in the trial, and critics said they should also demand disclosure of payment requirements, or outright ban such trials from the site.

Paul-Knoepfler-2013 “The average patient and even people in health care … kind of let their guard down when they’re in that database. It’s like, ‘If a trial is listed here, it must be OK,’” said Paul Knoepfler, a CIRM grantee and fellow blogger at the University of California, Davis. “Most people don’t realize that creeping into that database are some trials whose main goal is to generate profit.”

The NIH representative quoted in the article made it sound like the agency was open to making some changes. But no promises were made.

Added note 7/30. While this post factually describes an article that appeared in the mainstream media, the role of this column, I should add that while I did not take a position on paid trials, I am thrilled Stemgenex is collecting data and look forward to them sharing that data in a timely, peer-reviewed fashion.

 

Off the shelf T cells.  We at CIRM got some good news this week. We always like it when we see an announcement that technology from a researcher we have supported gets licensed to a company. That commercialization moves it a giant step closer to helping patients.

This week, Kite Pharma licensed a system developed in the lab of Gay Crooks at the University of California, Los Angeles, that creates an artificial thymus “organoid” in a dish capable of mass producing the immune system’s T cells from pluripotent stem cells. Just growing stem cells in the lab yields tiny amounts of T cells. They naturally mature in our bodies in the thymus gland, and seem to need that nurturing to thrive.

T-cell based immune therapy is all the rage now in cancer therapy because early trials are producing some pretty amazing results, and Kite is a leader in the field. But up until now those therapies have all been autologous—they used the patient’s own cells and manipulate them individually in the lab. That makes for a very expensive therapy. Kite sees the Crooks technology as a way to turn the procedure into an allogeneic one—using donor cells that could be pre-made for an “off-the-shelf” therapy. Their press release also envisioned adding some genetic manipulation to make the cells less likely to cause immune complications.

FierceBiotech published a bit more analysis of the deal, but we are not going to go into more detail on the actual science now. Crooks is finalizing publication of the work in a scientific journal, and when she does you can get the details here. Stay tuned.

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.


Related links:

Multi-Talented Stem Cells: The Many Ways to Use Them in the Clinic

CIRM kicked off the 2016 International Society for Stem Cell Research (ISSCR) Conference in San Francisco with a public stem cell event yesterday that brought scientists, patients, patient advocates and members of the general public together to discuss the many ways stem cells are being used in the clinic to develop treatments for patients with unmet medical needs.

Bruce Conklin, Gladstone Institutes & UCSF

Bruce Conklin, Gladstone Institutes & UCSF

Bruce Conklin, an Investigator at the Gladstone Institutes and UCSF Professor, moderated the panel of four scientists and three patient advocates. He immediately captured the audience’s attention by showing a stunning video of human heart cells, beating in synchrony in a petri dish. Conklin explained that scientists now have the skills and technology to generate human stem cell models of cardiomyopathy (heart disease) and many other diseases in a dish.

Conklin went on to highlight four main ways that stem cells are contributing to human therapy. First is using stem cells to model diseases whose causes are still largely unknown (like with Parkinson’s disease). Second, genome editing of stem cells is a new technology that has the potential to offer cures to patients with genetic disorders like sickle cell anemia. Third, stem cells are known to secrete healing factors, and transplanting them into humans could be beneficial. Lastly, stem cells can be engineered to attack cancer cells and overcome cancer’s normal way of evading the immune system.

Before introducing the other panelists, Conklin made the final point that stem cell models are powerful because scientists can use them to screen and develop new drugs for diseases that have no treatments or cures. His lab is already working on identifying new drugs for heart disease using human induced pluripotent stem cells derived from patients with cardiomyopathy.

Scientists and Patient Advocates Speak Out

Malin Parmar, Lund University

Malin Parmar, Lund University

The first scientist to speak was Malin Parmar, a Professor at Lund University. She discussed the history of stem cell development for clinical trials in Parkinson’s disease (PD). Her team is launching the first in-human trial for Parkinson’s using cells derived from human pluripotent stem cells in 2016. After Parmar’s talk, John Lipp, a PD patient advocate. He explained that while he might look normal standing in front of the crowd, his PD symptoms vary wildly throughout the day and make it hard for him to live a normal life. He believes in the work that scientists like Parmar are doing and confidently said, “In my lifetime, we will find a stem cell cure for Parkinson’s disease.”

Adrienne Shapiro, Patient Advocate

Adrienne Shapiro, Patient Advocate

The next scientist to speak was UCLA Professor Donald Kohn. He discussed his lab’s latest efforts to develop stem cell treatments for different blood disorder diseases. His team is using gene therapy to modify blood stem cells in bone marrow to treat and cure babies with SCID, also known as “bubble-boy disease”. Kohn also mentioned their work in sickle cell disease (SCD) and in chronic granulomatous disease, both of which are now in CIRM-funded clinical trials. He was followed by Adrienne Shapiro, a patient advocate and mother of a child with SCD. Adrienne gave a passionate and moving speech about her family history of SCD and her battle to help find a cure for her daughter. She said “nobody plans to be a patient advocate. It is a calling born of necessity and pain. I just wanted my daughter to outlive me.”

Henry Klassen (UC Irvine)

Henry Klassen, UC Irvine

Henry Klassen, a professor at UC Irvine, next spoke about blinding eye diseases, specifically retinitis pigmentosa (RP). This disease damages the photo receptors in the back of the eye and eventually causes blindness. There is no cure for RP, but Klassen and his team are testing the safety of transplanting human retinal progenitor cells in to the eyes of RP patients in a CIRM-funded Phase 1/2 clinical trial.

Kristen MacDonald, RP patient

Kristen MacDonald, RP patient

RP patient, Kristen MacDonald, was the trial’s first patient to be treated. She bravely spoke about her experience with losing her vision. She didn’t realize she was going blind until she had a series of accidents that left her with two broken arms. She had to reinvent herself both physically and emotionally, but now has hope that she might see again after participating in this clinical trial. She said that after the transplant she can now finally see light in her bad eye and her hope is that in her lifetime she can say, “One day, people used to go blind.”

Lastly, Catriona Jamieson, a professor and Alpha Stem Cell Clinic director at UCSD, discussed how she is trying to develop new treatments for blood cancers by eradicating cancer stem cells. Her team is conducting a Phase 1 CIRM-funded clinical trial that’s testing the safety of an antibody drug called Cirmtuzumab in patients with chronic lymphocytic leukemia (CLL).

Scientists and Patients need to work together

Don Kohn, Catriona Jamieson, Malin Parmar

Don Kohn, Catriona Jamieson, Malin Parmar

At the end of the night, the scientists and patient advocates took the stage to answer questions from the audience. A patient advocate in the audience asked, “How can we help scientists develop treatments for patients more quickly?”

The scientists responded that stem cell research needs more funding and that agencies like CIRM are making this possible. However, we need to keep the momentum going and to do that both the physicians, scientists and patient advocates need to work together to advocate for more support. The patient advocates in the panel couldn’t have agreed more and voiced their enthusiasm for working together with scientists and clinicians to make their hopes for cures a reality.

The CIRM public event was a huge success and brought in more than 150 people, many of whom stayed after the event to ask the panelists more questions. It was a great kick off for the ISSCR conference, which starts today. For coverage, you can follow the Stem Cellar Blog for updates on interesting stem cell stories that catch our eye.

CIRM Public Stem Cell Event

CIRM Public Stem Cell Event