A clear vision for the future

Dr. Henry Klassen and Dr. Jing Yang, founders of jCyte

When you have worked with a group of people over many years the relationship becomes more than just a business venture, it becomes personal. That’s certainly the case with jCyte, a company founded by Drs. Henry Klassen and Jing Yang, aimed at finding a cure for a rare form of vision loss called retinitis pigmentosa. CIRM has been supporting this work since it’s early days and so on Friday, the news that jCyte has entered into a partnership with global ophthalmology company Santen was definitely a cause for celebration.

The partnership could be worth up to $252 million and includes an immediate payment of $62 million. The agreement also connects jCyte to Santen’s global business and medical network, something that could prove invaluable in bringing their jCell therapy to patients outside the US.

Here in the US, jCyte is getting ready to start a Phase 2 clinical trial – which CIRM is funding – that could prove pivotal in helping it get approval from the US Food and Drug Administration.

As Dr. Maria Millan, CIRM’s President and CEO says, we have been fortunate to watch this company steadily progress from having a promising idea to developing a life-changing therapy.

“This is exciting news for everyone at jCyte. They have worked so hard over many years to develop their therapy and this partnership is a reflection of just how much they have achieved. For us at CIRM it’s particularly encouraging. We have supported this work from its early stages through clinical trials. The people who have benefited from the therapy, people like Rosie Barrero, are not just patients to us, they have become friends. The people who run the company, Dr. Henry Klassen, Dr. Jing Yang and CEO Paul Bresge, are so committed and so passionate about their work that they have overcome many obstacles to bring them here, an RMAT designation from the Food and Drug Administration, and a deal that will help them advance their work even further and faster. That is what CIRM is about, following the science and the mission.”

Paul Bresge, jCyte’s CEO says they couldn’t have done it without CIRM’s early and continued investment.

Paul Bresge, jCyte CEO

“jCyte is extremely grateful to CIRM, which was established to support innovative regenerative medicine programs and research such as ours.  CIRM supported our early preclinical data all the way through our late stage clinical trials.  This critical funding gave us the unique ability and flexibility to put patients first in each and every decision that we made along the way. In addition to the funding, the guidance that we have received from the CIRM team has been invaluable. jCell would not be possible without the early support from CIRM, our team at jCyte, and patients with degenerative retinal diseases are extremely appreciative for your support.”

Here is Rosie Barrero talking about the impact jCell has had on her life and the life of her family.

Helping the blind see – mice that is

When I first saw the headline for this story I thought of the nursery rhyme about the three blind mice. Finally, they’ll be able to see the farmer’s wife coming at them with a carving knife. But the real-world implications are of this are actually pretty exciting.

Researchers at the National Institute of Health’s National Eye Institute took skin cells from mice and directly reprogrammed them into becoming light sensitizing cells in the eye, the kind that are often damaged and destroyed by diseases like macular degeneration or retinitis pigmentosa.

What’s particularly interesting about this is that it bypassed the induced pluripotent stem cell (iPSC) stage where researchers turn the skin cells into embryonic-like cells, then turn those into the cells found in the eye.

In a news release, Anand Swaroop of the NEI says this more direct approach has a number of advantages: “This is the first study to show that direct, chemical reprogramming can produce retinal-like cells, which gives us a new and faster strategy for developing therapies for age-related macular degeneration and other retinal disorders caused by the loss of photoreceptors.”

After converting the skin cells into cells called rod photoreceptors – the light sensing cells found in the back of the eye – the team transplanted them into blind mice. One month later they tested the mice to see if there had been any change in vision. There had; 43 percent of the mice reacted to light exposure, something they hadn’t done before.

Biraj Mahato, the study’s first author, said that three months later, the transplanted cells were still alive and functioning. “Even mice with severely advanced retinal degeneration, with little chance of having living photoreceptors remaining, responded to transplantation. Such findings suggest that the observed improvements were due to the lab-made photoreceptors rather than to an ancillary effect that supported the health of the host’s existing photoreceptors.”

Obviously there is a lot of work still to do before we can even begin to think about trying something like this in people. But this is certainly an encouraging start.

In the meantime, CIRM is funding a number of stem cell programs aimed at treating vision destroying diseases like macular degeneration and retinitis pigmentosa.

Facebook Live: Ask the Stem Cell Team

On December 12th we hosted our latest ‘Facebook Live: Ask the Stem Cell Team’ event. This time around we really did mean team. We had a host of our Science Officers answering questions from friends and supporters of CIRM. We got a lot of questions and didn’t have enough time to address them all. So here’s answers to all the questions.

What are the obstacles to using partial cellular reprogramming to return people’s entire bodies to a youthful state. Paul Hartman.  San Leandro, California

Dr. Kelly Shepard

Dr. Kelly Shepard: Certainly, scientists have observed that various manipulations of cells, including reprogramming, partial reprogramming, de-differentiation and trans-differentiation, can restore or change properties of cells, and in some cases, these changes can reflect a more “youthful” state, such as having longer telomeres, better proliferative capacity, etc. However, some of these same rejuvenating properties, outside of their normal context, could be harmful or deadly, for example if a cell began to grow and divide when or where it shouldn’t, similar to cancer. For this reason, I believe the biggest obstacles to making this approach a reality are twofold: 1)  our current, limited understanding of the nature of partially reprogrammed cells; and 2) our inability to control the fate of those cells that have been partially reprogrammed, especially if they are inside a living organism.  Despite the challenges, I think there will be step wise advances where these types of approaches will be applied, starting with specific tissues. For example, CIRM has recently funded an approach that uses reprogramming to make “rejuvenated” versions of T cells for fighting lung cancer.  There is also a lot of interest in using such approaches to restore the reparative capacity of aged muscle. Perhaps some successes in these more limited areas will be the basis for expanding to a broader use.

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STROKE

What’s going on with Stanford’s stem cell trials for stroke? I remember the first trial went really well In 2016 have not heard anything about since? Elvis Arnold

Dr. Lila Collins

Dr. Lila Collins: Hi Elvis, this is an evolving story.  I believe you are referring to SanBio’s phase 1/2a stroke trial, for which Stanford was a site. This trial looked at the safety and feasibility of SanBio’s donor or allogeneic stem cell product in chronic stroke patients who still had motor deficits from their strokes, even after completing physical therapy when natural recovery has stabilized.  As you note, some of the treated subjects had promising motor recoveries. 

SanBio has since completed a larger, randomized phase 2b trial in stroke, and they have released the high-level results in a press release.  While the trial did not meet its primary endpoint of improving motor deficits in chronic stroke, SanBio conducted a very similar randomized trial in patients with stable motor deficits from chronic traumatic brain injury (TBI).  In this trial, SanBio saw positive results on motor recovery with their product.  In fact, this product is planned to move towards a conditional approval in Japan and has achieved expedited regulatory status in the US, termed RMAT, in TBI which means it could be available more quickly to patients if all goes well.  SanBio plans to continue to investigate their product in stroke, so I would stay tuned as the work unfolds. 

Also, since you mentioned Stanford, I should note that Dr Gary Steinberg, who was a clinical investigator in the SanBio trial you mentioned, will soon be conducting a trial with a different product that he is developing, neural progenitor cells, in chronic stroke.  The therapy looks promising in preclinical models and we are hopeful it will perform well for patients in the clinic.

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I am a stroke survivor will stem cell treatment able to restore my motor skills? Ruperto

Dr. Lila Collins:

Hi Ruperto. Restoring motor loss after stroke is a very active area of research.  I’ll touch upon a few ongoing stem cell trials.  I’d just like to please advise that you watch my colleague’s comments on stem cell clinics (these can be found towards the end of the blog) to be sure that any clinical research in which you participate is as safe as possible and regulated by FDA.

Back to stroke, I mentioned SanBio’s ongoing work to address motor skill loss in chronic stroke earlier.  UK based Reneuron is also conducting a phase 2 trial, using a neural progenitor cell as a candidate therapy to help recover persistent motor disability after stroke (chronic).  Dr Gary Steinberg at Stanford is also planning to conduct a clinical trial of a human embryonic stem cell-derived neuronal progenitor cell in stroke.

There is also promising work being sponsored by Athersys in acute stroke. Athersys published results from their randomized, double blinded placebo controlled Ph2 trial of their Multistem product in patients who had suffered a stroke within 24-48 hours.  After intravenous delivery, the cells improved a composite measure of stroke recovery, including motor recovery.  Rather than acting directly on the brain, Multistem seems to work by traveling to the spleen and reducing the inflammatory response to a stroke that can make the injury worse.

Athersys is currently recruiting a phase 3 trial of its Multistem product in acute stroke (within 1.5 days of the stroke).  The trial has an accelerated FDA designation, called RMAT and a special protocol assessment.  This means that if the trial is conducted as planned and it reaches the results agreed to with the FDA, the therapy could be cleared for marketing.  Results from this trial should be available in about two years. 

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Questions from several hemorrhagic stroke survivors who say most clinical trials are for people with ischemic strokes. Could stem cells help hemorrhagic stroke patients as well?

Dr. Lila Collins:

Regarding hemorrhagic stroke, you are correct the bulk of cell therapies for stroke target ischemic stroke, perhaps because this accounts for the vast bulk of strokes, about 85%.

That said, hemorrhagic strokes are not rare and tend to be more deadly.  These strokes are caused by bleeding into or around the brain which damages neurons.  They can even increase pressure in the skull causing further damage.  Because of this the immediate steps treating these strokes are aimed at addressing the initial bleeding insult and the blood in the brain.

While most therapies in development target ischemic stroke, successful therapies developed to repair neuronal damage or even some day replace lost neurons, could be beneficial after hemorrhagic stroke as well.

We are aware of a clinical trial targeting acute hemorrhagic stroke that is being run by the Mayo clinic in Jacksonville Florida.

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I had an Ischemic stroke in 2014, and my vision was also affected. Can stem cells possibly help with my vision issues. James Russell

Dr. Lila Collins:

Hi James. Vision loss from stroke is complex and the type of loss depends upon where the stroke occurred (in the actual eye, the optic nerve or to the other parts of the brain controlling they eye or interpreting vision).  The results could be:

  1. Visual loss from damage to the retina
  2. You could have a normal eye with damage to the area of the brain that controls the eye’s movement
  3. You could have damage to the part of the brain that interprets vision.

You can see that to address these various issues, we’d need different cell replacement approaches to repair the retina or the parts of the brain that were damaged. 

Replacing lost neurons is an active effort that at the moment is still in the research stages.  As you can imagine, this is complex because the neurons have to make just the right connections to be useful. 

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VISION

Is there any stem cell therapy for optical nerve damage? Deanna Rice

Dr. Ingrid Caras

Dr. Ingrid Caras: There is currently no proven stem cell therapy to treat optical nerve damage, even though there are shady stem cell clinics offering treatments.  However, there are some encouraging early gene therapy studies in mice using a virus called AAV to deliver growth factors that trigger regeneration of the damaged nerve. These studies suggest that it may be possible to restore at least some visual function in people blinded by optic nerve damage from glaucoma

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I read an article about ReNeuron’s retinitis pigmentosa clinical trial update.  In the article, it states: “The company’s treatment is a subretinal injection of human retinal progenitors — cells which have almost fully developed into photoreceptors, the light-sensing retinal cells that make vision possible.” My question is: If they can inject hRPC, why not fully developed photoreceptors? Leonard

Dr. Kelly Shepard: There is evidence from other studies, including from other tissue types such as blood, pancreas, heart and liver, that fully developed (mature) cell types tend not to engraft as well upon transplantation, that is the cells do not establish themselves and survive long term in their new environment. In contrast, it has been observed that cells in a slightly less “mature” state, such as those in the progenitor stage, are much more likely to establish themselves in a tissue, and then differentiate into more mature cell types over time. This question gets at the crux of a key issue for many new therapies, i.e. what is the best cell type to use, and the best timing to use it.

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My question for the “Ask the Stem Cell Team” event is: When will jCyte publish their Phase IIb clinical trial results. Chris Allen

Dr. Ingrid Caras: The results will be available sometime in 2020.

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I understand the hRPC cells are primarily neurotropic (rescue/halt cell death); however, the literature also says hRPC can become new photoreceptors.  My questions are: Approximately what percentage develop into functioning photoreceptors? And what percentage of the injected hRPC are currently surviving? Leonard Furber, an RP Patient

Dr. Kelly Shepard: While we can address these questions in the lab and in animal models, until there is a clinical trial, it is not possible to truly recreate the environment and stresses that the cells will undergo once they are transplanted into a human, into the site where they are expected to survive and function. Thus, the true answer to this question may not be known until after clinical trials are performed and the results can be evaluated. Even then, it is not always possible to monitor the fate of cells after transplantation without removing tissues to analyze (which may not be feasible), or without being able to transplant labeled cells that can be readily traced.

Dr. Ingrid Caras – Although the cells have been shown to be capable of developing into photoreceptors, we don’t know if this actually happens when the cells are injected into a patient’s eye.   The data so far suggest that the cells work predominantly by secreting growth factors that rescue damaged retinal cells or even reverse the damage. So one possible outcome is that the cells slow or prevent further deterioration of vision. But an additional possibility is that damaged retinal cells that are still alive but are not functioning properly may become healthy and functional again which could result in an improvement in vision.

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DIABETES

What advances have been made using stem cells for the treatment of Type 2 Diabetes? Mary Rizzo

Dr. Ross Okamura

Dr. Ross Okamura: Type 2 Diabetes (T2D) is a disease where the body is unable to maintain normal glucose levels due to either resistance to insulin-regulated control of blood sugar or insufficient insulin production from pancreatic beta cells.  The onset of disease has been associated with lifestyle influenced factors including body mass, stress, sleep apnea and physical activity, but it also appears to have a genetic component based upon its higher prevalence in certain populations. 

Type 1 Diabetes (T1D) differs from T2D in that in T1D patients the pancreatic beta cells have been destroyed by the body’s immune system and the requirement for insulin therapy is absolute upon disease onset rather than gradually developing over time as in many T2D cases.  Currently the only curative approach to alleviate the heavy burden of disease management in T1D has been donor pancreas or islet transplantation. However, the supply of donor tissue is small relative to the number of diabetic patients.  Donor islet and pancreas transplants also require immune suppressive drugs to prevent allogenic immune rejection and the use of these drugs carry additional health concerns.  However, for some patients with T1D, especially those who may develop potentially fatal hypoglycemia, immune suppression is worth the risk.

To address the issue of supply, there has been significant activity in stem cell research to produce insulin secreting beta cells from pluripotent stem cells and recent clinical data from Viacyte’s CIRM funded trial indicates that implanted allogeneic human stem cell derived cells in T1D patients can produce circulating c-peptide, a biomarker for insulin.  While the trial is not designed specifically to cure insulin-dependent T2D patients, the ability to produce and successfully engraft stem cell-derived beta cells would be able to help all insulin-dependent diabetic patients.

It’s also worth noting that there is a sound scientific reason to clinically test a patient-derived pluripotent stem cell-based insulin-producing cells in insulin-dependent T2D diabetic patients; the cells in this case could be evaluated for their ability to cure diabetes in the absence of needing to prevent both allogeneic and autoimmune responses.

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SPINAL CORD INJURY

Is there any news on clinical trials for spinal cord injury? Le Ly

Kevin McCormack: The clinical trial CIRM was funding, with Asterias (now part of a bigger company called Lineage Cell Therapeutics, is now completed and the results were quite encouraging. In a news release from November of 2019 Brian Culley, CEO of Lineage Cell Therapeutics, described the results this way.

“We remain extremely excited about the potential for OPC1 (the name of the therapy used) to provide enhanced motor recovery to patients with spinal cord injuries. We are not aware of any other investigative therapy for SCI (spinal cord injury) which has reported as encouraging clinical outcomes as OPC1, particularly with continued improvement beyond 1 year. Overall gains in motor function for the population assessed to date have continued, with Year 2 assessments measuring the same or higher than at Year 1. For example, 5 out of 6 Cohort 2 patients have recovered two or more motor levels on at least one side as of their Year 2 visit whereas 4 of 6 patients in this group had recovered two motor levels as of their Year 1 visit. To put these improvements into perspective, a one motor level gain means the ability to move one’s arm, which contributes to the ability to feed and clothe oneself or lift and transfer oneself from a wheelchair. These are tremendously meaningful improvements to quality of life and independence. Just as importantly, the overall safety of OPC1 has remained excellent and has been maintained 2 years following administration, as measured by MRI’s in patients who have had their Year 2 follow-up visits to date. We look forward to providing further updates on clinical data from SCiStar as patients continue to come in for their scheduled follow up visits.”

Lineage Cell Therapeutics plans to meet with the FDA in 2020 to discuss possible next steps for this therapy.

In the meantime the only other clinical trial I know that is still recruiting is one run by a company called Neuralstem. Here is a link to information about that trial on the www.clinicaltrials.gov website.

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ALS

Now that the Brainstorm ALS trial is finished looking for new patients do you have any idea how it’s going and when can we expect to see results? Angela Harrison Johnson

Dr. Ingrid Caras: The treated patients have to be followed for a period of time to assess how the therapy is working and then the data will need to be analyzed.  So we will not expect to see the results probably for another year or two.

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AUTISM

Are there treatments for autism or fragile x using stem cells? Magda Sedarous

Dr. Kelly Shepard: Autism and disorders on the autism spectrum represent a collection of many different disorders that share some common features, yet have different causes and manifestations, much of which we still do not understand. Knowing the origin of a disorder and how it affects cells and systems is the first step to developing new therapies. CIRM held a workshop on Autism in 2009 to brainstorm potential ways that stem cell research could have an impact. A major recommendation was to exploit stem cells and new technological advances to create cells and tissues, such as neurons, in the lab from autistic individuals that could then be studied in great detail.  CIRM followed this recommendation and funded several early-stage awards to investigate the basis of autism, including Rett Syndrome, Fragile X, Timothy Syndrome, and other spectrum disorders. While these newer investigations have not yet led to therapies that can be tested in humans, this remains an active area of investigation. Outside of CIRM funding, we are aware of more mature studies exploring the effects of umbilical cord blood or other specific stem cell types in treating autism, such as an ongoing clinical trial conducted at Duke University.

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PARKINSON’S DISEASE

What is happening with Parkinson’s research? Hanifa Gaphoor

Dr. Kent Fitzgerald

Dr. Kent Fitzgerald: Parkinson’s disease certainly has a significant amount of ongoing work in the regenerative medicine and stem cell research. 

The nature of cell loss in the brain, specifically the dopaminergic cells responsible for regulating the movement, has long been considered a good candidate for cell replacement therapy.  

This is largely due to the hypothesis that restoring function to these cells would reverse Parkinson’s symptoms. This makes a lot of sense as front line therapy for the disease for many years has been dopamine replacement through L-dopa pills etc.  Unfortunately, over time replacing dopamine through a pill loses its benefit, whereas replacing or fixing the cells themselves should be a more permanent fix. 

Because a specific population of cells in one part of the brain are lost in the disease, multiple labs and clinicians have sought to replace or augment these cells by transplantation of “new” functional cells able to restore function to the area an theoretically restore voluntary motor control to patients with Parkinson’s disease. 

Early clinical research showed some promise, however also yielded mixed results, using fetal tissue transplanted into the brains of Parkinson’s patients.   As it turns out, the cell types required to restore movement and avoid side effects are somewhat nuanced.  The field has moved away from fetal tissue and is currently pursuing the use of multiple stem cell types that are driven to what is believed to be the correct subtype of cell to repopulate the lost cells in the patient. 

One project CIRM sponsored in this area with Jeanne Loring sought to develop a cell replacement therapy using stem cells from the patients themselves that have been reprogrammed into the kinds of cell damaged by Parkinson’s.  This type of approach may ultimately avoid issues with the cells avoiding rejection by the immune system as can be seen with other types of transplants (i.e. liver, kidney, heart etc).

Still, others are using cutting edge gene therapy technology, like the clinical phase project CIRM is sponsoring with Krystof Bankiewicz to investigate the delivery of a gene (GDNF) to the brain that may help to restore the activity of neurons in the Parkinson’s brain that are no longer working as they should. 

The bulk of the work in the field of PD at the present remains centered on replacing or restoring the dopamine producing population of cells in the brain that are affected in disease.   

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HUNTINGTON’S DISEASE

Any plans for Huntington’s? Nikhat Kuchiki

Dr. Lisa Kadyk

Dr. Lisa Kadyk: The good news is that there are now several new therapeutic approaches to Huntington’s Disease that are at various stages of preclinical and clinical development, including some that are CIRM funded.   One CIRM-funded program led by Dr. Leslie Thompson at UC Irvine is developing a cell-based therapeutic that consists of neural stem cells that have been manufactured from embryonic stem cells.   When these cells are injected into the brain of a mouse that has a Huntington’s Disease mutation, the cells engraft and begin to differentiate into new neurons.  Improvements are seen in the behavioral and electrophysiological deficits in these mutant mice, suggesting that similar improvements might be seen in people with the disease.   Currently, CIRM is funding Dr. Thompson and her team to carry out rigorous safety studies in animals using these cells, in preparation for submitting an application to the FDA to test the therapy in human patients in a clinical trial.   

There are other, non-cell-based therapies also being tested in clinical trials now, using  anti-sense oligonucleotides (Ionis, Takeda) to lower the expression of the Huntington protein.  Another HTT-lowering approach is similar – but uses miRNAs to lower HTT levels (UniQure, Voyager)

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TRAUMATIC BRAIN INJURY (TBI)

My 2.5 year old son recently suffered a hypoxic brain injury resulting in motor and speech disabilities. There are several clinical trials underway for TBI in adults. My questions are:

  • Will the results be scalable to pediatric use and how long do you think it would take before it is available to children?
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  • I’m wondering why the current trials have chosen to go the route of intracranial injections as opposed to something slightly less invasive like an intrathecal injection?
  • Is there a time window period in which stem cells should be administered by, after which the administration is deemed not effective?

Dr. Kelly Shepard:  TBI and other injuries of the nervous system are characterized by a lot of inflammation at the time of injury, which is thought to interfere with the healing process- and thus some approaches are intended to be delivered after that inflammation subsides. However, we are aware of approaches that intend to deliver a therapy to a chronic injury, or one that has occurred  previously. Thus, the answer to this question may depend on how the intended therapy is supposed to work. For example, is the idea to grow new neurons, or is it to promote the survival of neurons of other cells that were spared by the injury? Is the therapy intended to address a specific symptom, such as seizures? Is the therapy intended to “fill a gap” left behind after inflammation subsides, which might not restore all function but might ameliorate certain symptoms.? There is still a lot we don’t understand about the brain and the highly sophisticated network of connections that cannot be reversed by only replacing neurons, or only reducing inflammation, etc. However, if trials are well designed, they should yield useful information even if the therapy is not as effective as hoped, and this information will pave the way to newer approaches and our technology and understanding evolves.

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We have had a doctor recommending administering just the growth factors derived from MSC stem cells. Does the science work that way? Is it possible to isolate the growth factors and boost the endogenous growth factors by injecting allogenic growth factors?

Dr. Stephen Lin

Dr. Stephen Lin:  Several groups have published studies on the therapeutic effects in non-human animal models of using nutrient media from MSC cultures that contain secreted factors, or extracellular vesicles from cells called exosomes that carry protein or nucleic acid factors.  Scientifically it is possible to isolate the factors that are responsible for the therapeutic effect, although to date no specific factor or combination of factors have been identified to mimic the effects of the undefined mixtures in the media and exosomes.  At present no regulatory approved clinical therapy has been developed using this approach. 

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PREDATORY STEM CELL CLINICS

What practical measures are being taken to address unethical practitioners whose bad surgeries are giving stem cell advances a bad reputation and are making forward research difficult? Kathy Jean Schultz

Dr. Geoff Lomax

Dr. Geoff Lomax: Terrific question! I have been doing quite a bit research into the history of this issue of unethical practitioners and I found an 1842 reference to “quack medicines.” Clearly this is nothing new. In that day, the author appealed to make society “acquainted with the facts.”

In California, we have taken steps to (1) acquaint patients with the facts about stem cell treatments and (2) advance FDA authorized treatments for unmet medical needs.

  • First, CIRM work with Senator Hernandez in 2017 to write a law the requires provides to disclose to patient that a stem cell therapy has not been approved by the Food and Drug administration.
  • We continue to work with the State Legislature and Medical Board of California to build on policies that require accurate disclosure of the facts to patients.
  • Second, our clinical trial network the — Alpha Stem Cell Clinics – have supported over 100 FDA-authorized clinical trials to advance responsible clinical research for unmet medical needs.

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I’m curious if adipose stem cell being used at clinics at various places in the country is helpful or beneficial? Cheri Hicks

Adipose tissue has been widely used particularly in plastic and reconstructive surgery. Many practitioners suggest adipose cells are beneficial in this context. With regard to regenerative medicine and / or the ability to treat disease and injury, I am not aware of any large randomized clinical trials that demonstrate the safety and efficacy of adipose-derived stem cells used in accordance with FDA guidelines.

I went to a “Luncheon about Stem Cell Injections”. It sounded promising. I went thru with it and got the injections because I was desperate from my knee pain. The price of stem cell injections was $3500 per knee injection. All went well. I have had no complications, but haven’t noticed any real major improvement, and here I am a year later. My questions are:

 1) I wonder on where the typical injection cells are coming from?

  2) I wonder what is the actual cost of the cells?

3) What kind of results are people getting from all these “pop up” clinics or established clinics that are adding this to there list of offerings?

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Dr. Geoff Lomax: You raise a number of questions and point here; they are all very good and it’s is hard to give a comprehensive response to each one, but here is my reaction:

  • There are many practitioners in the field of orthopedics who sincerely believe in the potential of cell-based treatments to treat injury / pain
  • Most of the evidence presented is case reports that individuals have benefited
  • The challenge we face is not know the exact type of injury and cell treatments used.
  • Well controlled clinical trials would really help us understand for what cells (or cell products) and for what injury would be helpful
  • Prices of $3000 to $5000 are not uncommon, and like other forms of private medicine there is often a considerable mark-up in relation to cost of goods.
  • You are correct that there have not been reports of serious injury for knee injections
  • However the effectiveness is not clear while simultaneously millions of people have been aided by knee replacements.

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Do stem cells have benefits for patients going through chemotherapy and radiation therapy? Ruperto

Dr. Kelly Shepard: The idea that a stem cell therapy could help address effects of chemotherapy or radiation is being and has been pursued by several investigators over the years, including some with CIRM support. Towards the earlier stages, people are looking at the ability of different stem cell-derived neural cell preparations to replace or restore function of certain brain cells that are damaged by the effects of chemotherapy or radiation. In a completely different type of approach, a group at City of Hope is exploring whether a bone marrow transplant with specially modified stem cells can provide a protective effect against the chemotherapy that is used to treat a form of brain cancer, glioblastoma. This study is in the final stage of development that, if all goes well, culminates with application to the FDA to allow initiation of a clinical trial to test in people.

Dr. Ingrid Caras: That’s an interesting and valid question.  There is a Phase 1 trial ongoing that is evaluating a novel type of stem/progenitor cell from the umbilical cord of healthy deliveries.  In animal studies, these cells have been shown to reduce the toxic effects of chemotherapy and radiation and to speed up recovery. These cells are now being tested in a First-in-human clinical trial in patients who are undergoing high-dose chemotherapy to treat their disease.

There is a researcher at Stanford, Michelle Monje, who is investigating that the role of damage to stem cells in the cognitive problems that sometimes arise after chemo- and radiation therapy (“chemobrain”).  It appears that damage to stem cells in the brain, especially those responsible for producing oligodendrocytes, contributes to chemobrain.  In CIRM-funded work, Dr. Monje has identified small molecules that may help prevent or ameliorate the symptoms of chemobrain.

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Is it possible to use a technique developed to fight one disease to also fight another? For instance, the bubble baby disease, which has cured (I think) more than 50 children, may also help fight sickle cell anemia?  Don Reed.

Dr. Lisa Kadyk: Hi Don. Yes, the same general technique can often be applied to more than one disease, although it needs to be “customized” for each disease.   In the example you cite, the technique is an “autologous gene-modified bone marrow transplant” – meaning the cells come from the patient themselves.  This technique is relevant for single gene mutations that cause diseases of the blood (hematopoietic) system.  For example, in the case of “bubble baby” diseases, a single mutation can cause failure of immune cell development, leaving the child unable to fight infections, hence the need to have them live in a sterile “bubble”.   To cure that disease, blood stem cells, which normally reside in the bone marrow, are collected from the patient and then a normal version of the defective gene is introduced into the cells, where it is incorporated into the chromosomes.   Then, the corrected stem cells are transplanted back into the patient’s body, where they can repopulate the blood system with cells expressing the normal copy of the gene, thus curing the disease.  

A similar approach could be used to treat sickle cell disease, since it is also caused by a single gene mutation in a gene (beta hemoglobin) that is expressed in blood cells.  The same technique would be used as I described for bubble baby disease but would differ in the gene that is introduced into the patient’s blood stem cells. 

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Is there any concern that CIRM’s lack of support in basic research will hamper the amount of new approaches that can reach clinical stages? Jason

Dr. Kelly Shepard: CIRM always has and continues to believe that basic research is vital to the field of regenerative medicine. Over the past 10 years CIRM has invested $904 million in “discovery stage/basic research”, and about $215 million in training grants that supported graduate students, post docs, clinical fellows, undergraduate, masters and high school students performing basic stem cell research. In the past couple of years, with only a limited amount of funds remaining, CIRM made a decision to invest most of the remaining funds into later stage projects, to support them through the difficult transition from bench to bedside. However, even now, CIRM continues to sponsor some basic research through its Bridges and SPARK Training Grant programs, where undergraduate, masters and even high school students are conducting stem cell research in world class stem cell laboratories, many of which are the same laboratories that were supported through CIRM basic research grants over the past 10 years. While basic stem cell research continues to receive a substantial level of support from the NIH ($1.8 billion in 2018, comprehensively on stem cell projects) and other funders, CIRM believes continued support for basic research, especially in key areas of stem cell research and vital opportunities, will always be important for discovering and developing new treatments.

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What is the future of the use of crispr cas9 in clinical trials in california/globally. Art Venegas

Dr. Kelly Shepard: CRISPR/Cas9 is a powerful gene editing tool. In only a few years, CRISPR/Cas9 technology has taken the field by storm and there are already a few CRISPR/Cas9 based treatments being tested in clinical trials in the US. There are also several new treatments that are at the IND enabling stage of development, which is the final testing stage required by the FDA before a clinical trial can begin. Most of these clinical trials involving CRISPR go through an “ex vivo” approach, taking cells from the patient with a disease causing gene, correcting the gene in the laboratory using CRISPR, and reintroducing the cells carrying the corrected gene back into the patient for treatment.  Sickle cell disease is a prime example of a therapy being developed using this strategy and CIRM funds two projects that are preparing for clinical trials with this approach.  CRISPR is also being used to develop the next generation of cancer T-cell therapies (e.g. CAR-T), where T-cells – a vital part of our immune system – are modified to target and destroy cancer cell populations.  Using CRISPR to edit cells directly in patients “in vivo” (inside the body) is far less common currently but is also being developed.  It is important to note that any FDA sanctioned “in vivo” CRISPR clinical trial in people will only modify organ-specific cells where the benefits cannot be passed on to subsequent generations. There is a ban on funding for what are called germ line cells, where any changes could be passed down to future generations.

CIRM is currently supporting multiple CRISPR/Cas9 gene editing projects in California from the discovery or most basic stage of research, through the later stages before applying to test the technique in people in a clinical trial.

While the field is new – if early safety signals from the pioneering trials are good, we might expect a number of new CRISPR-based approaches to enter clinical testing over the next few years. The first of these will will likely be in the areas of bone marrow transplant to correct certain blood/immune or  metabolic diseases, and cancer immunotherapies, as these types of approaches are the best studied and furthest along in the pipeline.

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Explain the differences between gene therapy and stem cell therapy? Renee Konkol

Dr. Stephen Lin:  Gene therapy is the direct modification of cells in a patient to treat a disease.  Most gene therapies use modified, harmless viruses to deliver the gene into the patient.  Gene therapy has recently seen many success in the clinic, with the first FDA approved therapy for a gene induced form of blindness in 2017 and other approvals for genetic forms of smooth muscle atrophy and amyloidosis. 

Stem cell therapy is the introduction of stem cells into patients to treat a disease, usually with the purpose of replacing damaged or defective cells that contribute to the disease.  Stem cell therapies can be derived from pluripotent cells that have the potential to turn into any cell in the body and are directed towards a specific organ lineage for the therapy.  Stem cell therapies can also be derived from other cells, called progenitors, that have the ability to turn into a limited number of other cells in the body. for example hematopoietic or blood stem cells (HSCs), which are found in bone marrow, can turn into other cells of the blood system including B-cells and T-cells: while mesenchymal stem cells (MSCs), which are usually found in fat tissue, can turn into bone, cartilage, and fat cells.  The source of these cells can be from the patient’s own body (autologous) or from another person (allogeneic).

Gene therapy is often used in combination with cell therapies when cells are taken from the patient and, in the lab, modified genetically to correct the mutation or to insert a correct form of the defective gene, before being returned to patients.  Often referred to as “ex vivo gene therapy” – because the changes are made outside the patient’s body – these therapies include Chimeric Antigen Receptor T (CAR-T) cells for cancer therapy and gene modified HSCs to treat blood disorders such as severe combined immunodeficiency and sickle cell disease. This is an exciting area that has significantly improved and even cured many people already.

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Currently, how can the outcome of CIRM stem cell medicine projects and clinical trials be soundly interpreted when their stem cell-specific doses are not known? James L. Sherley, M.D., Ph.D., Director. Asymmetrex, LLC

Dr. Stephen Lin:  Stem cell therapies that receive approval to conduct clinical trials must submit a package of data to the FDA that includes studies that demonstrate their effectiveness, usually in animal models of the disease that the cell therapy is targeting.  Those studies have data on the dose of the cell therapy that creates the therapeutic effect, which is used to estimate cell doses for the clinical trial.  CIRM funds discovery and translational stage awards to conduct these types of studies to prepare cell therapies for clinical trials.  The clinical trial is also often designed to test multiple doses of the cell therapy to determine the one that has the best therapeutic effect.   Dosing can be very challenging with cell therapies because of issues including survival, engraftment, and immune rejection, but CIRM supports studies designed to provide data to give the best estimate possible.

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Is there any research on using stem cells to increase the length of long bones in people?” For example, injecting stem cells into the growth plates to see if the cells can be used to lengthen limbs. Sajid

Dr. Kelly Shepard: There is quite a lot of ongoing research seeking ways to repair bones with stem cell based approaches, which is not the same but somewhat related. Much of this is geared towards repairing the types of bone injuries that do not heal well naturally on their own (large gaps, dead bone lesions, degenerative bone conditions). Also, a lot of this research involves engineering bone tissues in the lab and introducing the engineered tissue into a bone lesion that need be repaired. What occurs naturally at the growth plate is a complex interaction between many different cell types, much of which we do not fully understand. We do not fully understand how to use the cells that are used to engineer bone tissue in the lab. However, a group at Stanford, with some CIRM support, recently discovered a “skeletal stem cell” that exists naturally at the ends of human bones and at sites of fracture.  These are quite different than MSCs and offer a new path to be explored for repairing and generating bone. 

Stem Cell Agency Approves Funding for Clinical Trials Targeting Parkinson’s Disease and Blindness

The governing Board of the California Institute for Regenerative Medicine (CIRM) yesterday invested $32.92 million to fund the Stem Cell Agency’s first clinical trial in Parkinson’s disease (PD), and to support three clinical trials targeting different forms of vision loss.

This brings the total number of clinical trials funded by CIRM to 60.

The PD trial will be carried out by Dr. Krystof Bankiewicz at Brain Neurotherapy Bio, Inc. He is using a gene therapy approach to promote the production of a protein called GDNF, which is best known for its ability to protect dopaminergic neurons, the kind of cell damaged by Parkinson’s. The approach seeks to increase dopamine production in the brain, alleviating PD symptoms and potentially slowing down the disease progress.

David Higgins, PhD, a CIRM Board member and patient advocate for Parkinson’s says there is a real need for new approaches to treating the disease. In the US alone, approximately 60,000 people are diagnosed with PD each year and it is expected that almost one million people will be living with the disease by 2020.

“Parkinson’s Disease is a serious unmet medical need and, for reasons we don’t fully understand, its prevalence is increasing. There’s always more outstanding research to fund than there is money to fund it. The GDNF approach represents one ‘class’ of potential therapies for Parkinson’s Disease and has the potential to address issues that are even broader than this specific therapy alone.”

The Board also approved funding for two clinical trials targeting retinitis pigmentosa (RP), a blinding eye disease that affects approximately 150,000 individuals in the US and 1.5 million people around the world. It is caused by the destruction of light-sensing cells in the back of the eye known as photoreceptors.  This leads to gradual vision loss and eventually blindness.  There are currently no effective treatments for RP.

Dr. Henry Klassen and his team at jCyte are injecting human retinal progenitor cells (hRPCs), into the vitreous cavity, a gel-filled space located in between the front and back part of the eye. The proposed mechanism of action is that hRPCs secrete neurotrophic factors that preserve, protect and even reactivate the photoreceptors, reversing the course of the disease.

CIRM has supported early development of Dr. Klassen’s approach as well as preclinical studies and two previous clinical trials.  The US Food and Drug Administration (FDA) has granted jCyte Regenerative Medicine Advanced Therapy (RMAT) designation based on the early clinical data for this severe unmet medical need, thus making the program eligible for expedited review and approval.

The other project targeting RP is led by Dr. Clive Svendsen from the Cedars-Sinai Regenerative Medicine Institute. In this approach, human neural progenitor cells (hNPCs) are transplanted to the back of the eye of RP patients. The goal is that the transplanted hNPCs will integrate and create a protective layer of cells that prevent destruction of the adjacent photoreceptors. 

The third trial focused on vision destroying diseases is led by Dr. Sophie Deng at the University of California Los Angeles (UCLA). Dr. Deng’s clinical trial addresses blinding corneal disease by targeting limbal stem cell deficiency (LSCD). Under healthy conditions, limbal stem cells (LSCs) continuously regenerate the cornea, the clear front surface of the eye that refracts light entering the eye and is responsible for the majority of the optical power. Without adequate limbal cells , inflammation, scarring, eye pain, loss of corneal clarity and gradual vision loss can occur. Dr. Deng’s team will expand the patient’s own remaining LSCs for transplantation and will use  novel diagnostic methods to assess the severity of LSCD and patient responses to treatment. This clinical trial builds upon previous CIRM-funded work, which includes early translational and late stage preclinical projects.

“CIRM funds and accelerates promising early stage research, through development and to clinical trials,” says Maria T. Millan, MD, President and CEO of CIRM. “Programs, such as those funded today, that were novel stem cell or gene therapy approaches addressing a small number of patients, often have difficulty attracting early investment and funding. CIRM’s role is to de-risk these novel regenerative medicine approaches that are based on rigorous science and have the potential to address unmet medical needs. By de-risking programs, CIRM has enabled our portfolio programs to gain significant downstream industry funding and partnership.”

CIRM Board also awarded $5.53 million to Dr. Rosa Bacchetta at Stanford to complete work necessary to conduct a clinical trial for IPEX syndrome, a rare disease caused by mutations in the FOXP3 gene. Immune cells called regulatory T Cells normally function to protect tissues from damage but in patients with IPEX syndrome, lack of functional Tregs render the body’s own tissues and organs to autoimmune attack that could be fatal in early childhood.  Current treatment options include a bone marrow transplant which is limited by available donors and graft versus host disease and immune suppressive drugs that are only partially effective. Dr. Rosa Bacchetta and her team at Stanford will use gene therapy to insert a normal version of the FOXP3 gene into the patient’s own T Cells to restore the normal function of regulatory T Cells.

The CIRM Board also approved investing $15.80 million in four awards in the Translational Research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.

The TRAN1 Awards are summarized in the table below:

ApplicationTitleInstitutionAward Amount
TRAN1 11536Ex Vivo Gene Editing of Human Hematopoietic Stem Cells for the Treatment of X-Linked Hyper IgM Syndrome  UCLA $4,896,628
TRAN1 11555BCMA/CS1 Bispecific CAR-T Cell Therapy to Prevent Antigen Escape in Multiple Myeloma  UCLA $3,176,805
TRAN1 11544 Neural Stem cell-mediated oncolytic immunotherapy for ovarian cancer  City of Hope $2,873,262
TRAN1 11611Development of a human stem cell-derived inhibitory neuron therapeutic for the treatment of chronic focal epilepsyNeurona Therapeutics$4,848,750

Breaking bad news to stem cell researchers

It’s never easy to tell someone that they are too late, that they missed the deadline. It’s particularly hard when you know that the person you are telling that to has spent years working on a project and now needs money to take it to the next level. But in science, as in life, it’s always better to tell people what they need to know rather than what they would like to hear.

And so, we have posted a notice on our website for researchers thinking about applying for funding that, except in a very few cases, they are too late, that there is no money available for new projects, whether it’s Discovery, Translational or Clinical.

Here’s that notice:

CIRM anticipates that the budget allocation of funds for new awards under the CIRM clinical program (CLIN1, CLIN2 and CLIN3) may be depleted within the next two to three months. CIRM will accept applications for the monthly deadline on June 28, 2019 but will suspend application submissions after that date until further notice. All applicants should note that the review of submitted applications may be halted at any point in the process if funds are depleted prior to completion of the 3-month review cycle. CIRM will notify applicants of such an occurrence. Therefore, submission and acceptance of an application to CIRM does not guarantee the availability of funds or completion of a review cycle.

The submission of applications for the CIRM/NHLBI Cure Sickle Cell Initiative (CLIN1 SCD, CLIN2 SCD) are unaffected and application submissions for this program will remain open.

We do, of course, have enough money set aside to continue funding all the projects our Board has already approved, but we don’t have money for new projects (except for some sickle cell disease projects).

In truth our funding has lasted a lot longer than anyone anticipated. When Proposition 71 was approved the plan was to give CIRM $300 million a year for ten years. That was back in 2004. So what happened?

Well, in the early years stem cell science was still very much in its infancy with most of the work being done at a basic or Discovery level. Those typically don’t require very large sums so we were able to fund many projects without hitting our $300m target. As the field progressed, however, more and more projects were at the clinical trial stage and those need multiple millions of dollars to be completed. So, the money went out faster.

To date we have funded 55 clinical trials and our early support has helped more than a dozen other projects get into clinical trials. This includes everything from cancer and stroke, to vision loss and diabetes. It’s a good start, but we feel there is so much more to do.

Followers of news about CIRM know there is talk about a possible ballot initiative next year that would provide another $5.5 billion in funding for us to help complete the mission we have started.

Over the years we have built a pipeline of promising projects and without continued support many of those projects face a difficult future. Funding at the federal level is under threat and without CIRM there will be a limited number of funding alternatives for them to turn to.

Telling researchers we don’t have any money to support their work is hard. Telling patients we don’t have any money to support work that could lead to new treatments for them, that’s hardest of all.

Stem Cell Agency’s Diane Winokur hailed as Visionary

Diane and JT

CIRM Board member Diane Winokur with CIRM Board Chair Jonathan Thomas at FFB Awards dinner

Generally speaking, I am not a huge fan of gala dinners. It’s not that I don’t like seeing people who do remarkable things getting a well-deserved honor. It’s just that the dinners often go on too long and the food is usually not very good (hey, this is San Francisco, those things matter). But last night’s Foundation Fighting Blindness Visionary Awards in San Francisco was definitely an exception to that rule.

Academy of Sciences Grand Opening

Academy of Sciences in San Francisco

Now it may be that the awards were held in the spectacular Academy of Sciences building in Golden Gate Park, or that the food was delicious. But I think the real reason is that CIRM Board member Diane Winokur was one of those being honored. The other honoree was Dr. Jacque Duncan, an amazing physician at UC San Francisco who has dedicated her life to battling diseases of the retina. The whole event was deeply emotional, and truly inspiring.

Now, Diane is a remarkable woman in many respects. She’s the Board’s Patient Advocate member for ALS (better known as Lou Gehrig’s disease) and multiple sclerosis. But Diane also considers herself a Patient Advocate for all Californians and works hard to help advance the research that could help them. She has a personal connection to vision loss as well; one of her dear friends has lost his sight because of retinitis pigmentosa, and his daughter is losing hers because of the same disease.

Diane at podiumDiane highlighted the work that CIRM is doing to help battle vision destroying diseases; how we have invested more than $125 million in 25 different projects. She talked about the encouraging news from clinical trials we are funding targeting retinitis pigmentosa and dry age-related macular degeneration. Diane said:

“These stem cell clinical trials show that progress is being made. Not as fast as we would like, but as everyone here knows, good science takes time. As a patient advocate on the CIRM Board it’s my role to represent the patient, to be their voice in making decisions about what projects to fund.

Patients are at the heart of everything we do at CIRM, from deciding on funding issues to supporting clinical trials. That’s why I feel so honored to get this award. It comes from an organization, that is equally committed to doing all it can to help people in need, to putting the patient at the center of everything they do.”

It’s clear that patients really are at the heart of the work the Foundation Fighting Blindness (FFB) does. As the organizations CEO Benjamin Yerxa said:

“We support 77 labs in the US, often funding projects no one else would. We do this because we know it is necessary to advance the field. And we are going to keep doing this as best we can, as fast as we can, for as long as we can, because we know so many people are depending on us to help them.”

The other honoree, Jacque Duncan, said after attending many previous Visionary Award dinners and seeing the people being honored it was humbling to be in that company. She talked about the exciting progress being made in the field and the people who are making it possible.

“None of this happens by chance. The path to developing new treatments takes the passion of scientists and doctors, and the commitment of patients to raising the funds needed to do this research. One gala dinner at a time, one Vision Walk at a time. All of this creates community and a common purpose. I truly believe that because of this, tomorrow will be brighter than today.”

Perhaps it’s only appropriate to leave the last word to Diane, who ended her speech saying:

“The Nobel prize winning physicist Heinrich Rohrer once said that science means constantly walking a tightrope between blind faith and curiosity; between expertise and creativity; between bias and openness; between experience and epiphany; in short, between an old today and a new tomorrow.

I believe that working together, CIRM and the Foundation Fighting Blindness, we can create that new tomorrow.”

jCyte Shares Encouraging Update on Clinical Trial for Retinitis Pigmentosa

Stepping out of the darkness into light. That’s how patients are describing their experience after participating in a CIRM-funded clinical trial targeting a rare form of vision loss called retinitis pigmentosa (RP). jCyte, the company conducting the trial, announced 12 month results for its candidate stem cell-based treatment for RP.

RP is a genetic disorder that affects approximately 1 in 40,000 individuals and 1.5 million people globally. It causes the destruction of the light-sensing cells at the back of the eye called photoreceptors. Patients experience symptoms of vision loss starting in their teenage years and eventually become legally blind by middle age. While there is no cure for RP, there is hope that stem cell-based therapies could slow its progression in patients.

Photoreceptors look healthy in a normal retina (left). Cells are damaged in the retina of an RP patient (right). (Source National Eye Institute)

jCyte is one of the leaders in developing cell-based therapies for RP. The company, which was founded by UC Irvine scientists led by Dr. Henry Klassen, is testing a product called jCell, which is composed of pluripotent stem cell-derived progenitor cells that develop into photoreceptors. When transplanted into the back of the eye, they are believed to release growth factors that prevent further damage to the surviving cells in the retina. They also can integrate into the patient’s retina and develop into new photoreceptor cells to improve a patient’s vision.

Positive Results

At the Annual Ophthalmology Innovation Summit in November, jCyte announced results from its Phase 1/2a trial, which was a 12-month study testing two different doses of transplanted cells in 28 patients. The company reported a “favorable safety profile and indications of potential benefit” to patient vision.

The patients received a single injection of cells in their worst eye and their visual acuity (how well they can see) was then compared between the treated and untreated eye. Patients who received the lower dose of 0.5 million cells were able to see one extra letter on an eye chart with their treated eye compared to their untreated eye while patients that received the larger dose of 3 million cells were able to read 9 more letters. Importantly, none of the patients experienced any significant side effects from the treatment.

According to the company’s news release, “patient feedback was particularly encouraging. Many reported improved vision, including increased sensitivity to light, improved color discrimination and reading ability and better mobility. In addition, 22 of the 28 patients have been treated in their other eye as part of a follow-on extension study.”

One of these patients is Rosie Barrero. She spoke to us earlier this year about how the jCyte trial has not only improved her vision but has also given her hope. You can watch her video below.

Next Steps

These results suggest that the jCell therapy is safe (at least at the one year mark) to use in patients and that larger doses of jCell are more effective at improving vision in patients. jCyte CEO, Paul Bresge commented on the trial’s positive results:

Paul Bresge

“We are very encouraged by these results. Currently, there are no effective therapies to offer patients with RP. We are moving forward as quickly as possible to remedy that. The feedback we’ve received from trial participants has been remarkable. We look forward to moving through the regulatory process and bringing this easily-administered potential therapy to patients worldwide.”

Bresge and his company will be able to navigate jCell through the regulatory process more smoothly with the product’s recent Regenerative Medicine Advanced Therapy (RMAT) designation from the US Food and Drug Administration (FDA). The FDA grants RMAT to regenerative medicine therapies for serious diseases that have shown promise in early-stage clinical trials. The designation allows therapies to receive expedited review as they navigate their way towards commercialization.

jCyte is now evaluating the safety and efficacy of jCell in a Phase2b trial in a larger group of up to 85 patients. CIRM is also funding this trial and you can read more about it on our website.


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A Patient Advocate’s Personal Manifesto

Janni and Obama

President Obama and Janni Lehrer-Stein

Janni Lehrer-Stein was just 26 when she was diagnosed with a degenerative eye disease and told she was going to be blind within six months. The doctor who gave her the news told her “But don’t worry, people like you are usually hit and killed by a bus long before they go completely blind.”

At the time she was recently married, had just graduated law school and landed her dream job with the government in Washington DC, litigating workplace discrimination. The news about her eyesight stopped her in her tracks.

But not for long. If you ever met Janni you would know that nothing stops her for long.

I was fortunate enough to hear Janni talk at a Foundation Fighting Blindness event in the San Francisco Bay Area last weekend. I was part of a panel discussion on new approaches to treating vision loss, including the research that CIRM is funding.

Janni didn’t talk about stem cells, instead she focused on the importance of the patient advocate voice, community, and their determination. She said one of the most important things anyone battling a life-threatening or life-changing disease or disorder needs to remember is that it’s not about disability, it’s about capability. It’s about what you can do rather than what you cannot.

Janni laid out her “manifesto” for things she says will help you keep that thought uppermost in your mind.

1) Show up. It’s that simple and that important. You have to show up. You have to get educated, you have to learn all you can about your condition so you know what you can do and what you can’t do. You have to share that information with others. You have to be there for others. Don’t just show up for yourself. Show up for others who can’t be there.

2) Share this information. Janni talked about a website called My Retina Tracker which is helping drive research into the causes of retinal diseases like retinitis pigmentosa and macular degeneration, and hopefully will lead to treatments and even cures. She says the more people work together, the more we combine our resources, the more effective we can be.

3) Support the researchers. Janni says while raising awareness is important, raising money is just as important. Without money there can be no research, and without research no treatments or cures. Janni says it doesn’t matter how you do it – a charity walk, a Go Fund me campaign, petitioning your state or federal elected representatives to urge them to fund research – everything counts, every dollar helps.

4) Remember you are part of a wider community. Janni says no one ever won a battle on their own; it takes a lot of people to fight and win the right to be treated equally. And it takes a lot of effort to stop those rights from being rolled back.

Janni hasn’t let losing her sight hold her back. In 2011, she was appointed by President Obama, and confirmed by the U.S. Senate, to the National Council on Disability where she served two terms advising the President and Congress on national disability policy.

Now she has returned home to the San Francisco Bay Area, but she is no less determined to make a difference and no less determined to fight for the rights of patients and patient advocates.

In an article on Medium she shares her feelings about being a patient advocate:

“The America that I so deeply respect is one that embraces, values and respects the contributions of us all. My America includes every one of us, regardless of our gender, race, age or disability. Our America is a place where, regardless of whether we are sighted or blind, we have the same opportunities, for which we are equally considered. Our America includes every one of us who wishes to make the world a more peaceful, responsible, and inclusive environment that is tolerant of all differences and abilities, physical or otherwise. To me, those differences make our lives richer, give our contributions more meaning, and lead to a brighter future for the next generation.”

 

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.

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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