Texas tries to go it alone in offering unproven stem cell therapies to patients

Texas Capitol. (Shutterstock)

One of the most hotly debated topics in stem cell research is whether patients should be able to have easier access to unproven therapies using their own stem cells, at their own risk, and their own cost. It’s a debate that is dividing patients and physicians, researchers and lawmakers.

In California, a bill working its way through the state legislature wants to have warning signs posted in clinics offering unproven stem cell therapies, letting patients know they are potentially putting themselves at risk.

Texas is taking a very different approach. A series of bills under consideration would make it easier for clinics to offer unproven treatments; make it easier for patients with chronic illnesses to use the “right to try” law to take part in early-stage clinical trials (in the past, it was only patients with a terminal illness who could do that); and allow these clinics to charge patients for these unproven stem cell therapies.

Not surprisingly, the Texas bills are attracting some widely divergent views. Many stem cell researchers and some patient advocates are opposed to them, saying they prey on the needs of vulnerable people, offering them treatments – often costing thousands, even tens of thousands of dollars – that have little or no chance of success.

In an article on STATnews, Sean Morrison, a stem cell researcher at the University of Texas Southwestern Medical Center, in Dallas, said the Texas bills would be bad for patients:

“When patients get desperate, they have a capacity to suspend disbelief. When offered the opportunity of a therapy they believe in, even without data and if the chances of benefit are low, they’ll fight for access to that therapy. The problem is there are fraudulent stem cell clinics that have sprung up to exploit that.”

Patients like Jennifer Ziegler disagree with that completely. Ziegler has multiple sclerosis and has undergone three separate stem cell treatments – two in the US and one in Panama – to help treat her condition. She is also a founding member of Patients For Stem Cells (PFSC):

Jennifer Ziegler

“PFSC does not believe our cells are drugs. We consider the lack of access to adult stem cells an overreach by the federal government into our medical freedoms. My cells are not mass produced, and they do not cross state lines. An adult stem cell treatment is a medical procedure, between me, a fully educated patient, and my fully competent doctor.”

The issue is further complicated because the US Food and Drug Administration (FDA) – which has regulatory authority over stem cell treatments – considers the kinds of therapies these clinics offer to be a technical violation of the law. So even if Texas passes these three bills, they could still be in violation of federal law. However, a recent study in Cell Stem Cell showed that there are some 570 clinics around the US offering these unproven therapies, and to date the FDA has shown little inclination to enforce the law and shut those clinics down.

UC Davis stem cell researcher – and CIRM grantee – Paul Knoepfler is one of the co-authors of the study detailing how many clinics there are in the US. On his blog – The Niche – he recently expressed grave concerns about the Texas bills:

Paul Knoepfler

“The Texas Legislature is considering three risky bills that would give free rein to stem cell clinics to profit big time off of patients by selling unproven and unapproved “stem cell treatments” that have little if any science behind them. I call one of these bills “Right to Profit” for clinics, which if these became law could get millions from vulnerable patients and potentially block patient rights.”

Ziegler counters that patients have the right to try and save their own lives, saying if the Texas bills pass: “chronically ill, no option patients in the US, will have the opportunity to seek treatment without having to leave the country.”

It’s a debate we are all too familiar with at CIRM. Every day we get emails and phone calls from people asking for help in finding a treatment, for them or a loved one, suffering from a life-threatening or life-altering disease or disorder. It’s incredibly difficult having to tell them there is nothing that would help them currently being tested in a clinical trial.

Inevitably they ask about treatments they have seen online, offered by clinics using the patient’s own stem cells to treat them. At that point, it is no longer an academic debate about proven or unproven therapies, it has become personal; one person asking another for help, to find something, anything, to save their life.

Barring a dramatic change of policy at the FDA. these clinics are not going to go away. Nor will the need of patients who have run out of options and are willing to try anything to ease their pain or delay death. We need to find another way, one that brings these clinics into the fold and makes the treatments they offer part of the clinical trial process.

There are no easy answers, no simple solutions. But standing on either side of the divide, saying those on the other side are either “heartless” or “foolish” serves no one, helps no one. We need to figure out another way.

Positively good news from Asterias for CIRM-funded stem cell clinical trial for spinal cord injury

AsteriasWhenever I give a talk on stem cells one of the questions I invariably get asked is “how do you know the cells are going where you want them to and doing what you want them to?”

The answer is pretty simple: you look. That’s what Asterias Biotherapeutics did in their clinical trial to treat people with spinal cord injuries. They used magnetic resonance imaging (MRI) scans to see what was happening at the injury site; and what they saw was very encouraging.

Asterias is transplanting what they call AST-OPC1 cells into patients who have suffered recent injuries that have left them paralyzed from the neck down.  AST-OPC1 are oligodendrocyte progenitor cells, which develop into cells that support and protect nerve cells in the central nervous system, the area damaged in spinal cord injury. It’s hoped the treatment will restore connections at the injury site, allowing patients to regain some movement and feeling.

Taking a closer look

Early results suggest the therapy is doing just that, and now follow-up studies, using MRIs, are adding weight to those findings.

The MRIs – taken six months after treatment – show that the five patients given a dose of 10 million AST-OPC1 cells had no evidence of lesion cavities in their spines. That’s important because often, after a spinal cord injury, the injury site expands and forms a cavity, caused by the death of nerve and support cells in the spine, that results in permanent loss of movement and function below the site, and additional neurological damage to the patient.

Another group of patients, treated in an earlier phase of the clinical trial, showed no signs of lesion cavities 12 months after their treatment.

Positively encouraging

In a news release, Dr. Edward Wirth, the Chief Medical Officer at Asterias, says this is very positive:

“These new follow-up results based on MRI scans are very encouraging, and strongly suggest that AST-OPC1 cells have engrafted in these patients post-implantation and have the potential to prevent lesion cavity formation, possibly reducing long-term spinal cord tissue deterioration after spinal cord injury.”

Because the safety data is also encouraging Asterias is now doubling the dose of cells that will be transplanted into patients to 20 million, in a separate arm of the trial. They are hopeful this dose will be even more effective in helping restore movement and function in patients.

We can’t wait to see what they find.

Stem cell stories that caught our eye: update on Capricor’s heart attack trial; lithium on the brain; and how stem cells do math

Capricor ALLSTARToday our partners Capricor Therapeutics announced that its stem cell therapy for patients who have experienced a large heart attack is unlikely to meet one of its key goals, namely reducing the scar size in the heart 12 months after treatment.

The news came after analyzing results from patients at the halfway point of the trial, six months after their treatment in the Phase 2 ALLSTAR clinical trial which CIRM was funding. They found that there was no significant difference in the reduction in scarring on the heart for patients treated with donor heart-derived stem cells, compared to patients given a placebo.

Obviously this is disappointing news for everyone involved, but we know that not all clinical trials are going to be successful. CIRM supported this research because it clearly addressed an unmet medical need and because an earlier Phase 1 study had showed promise in helping prevent decline in heart function after a heart attack.

Yet even with this failure to repeat that promise in this trial,  we learned valuable lessons.

In a news release, Dr. Tim Henry, Director of the Division of Interventional Technologies in the Heart Institute at Cedars-Sinai Medical Center and a Co-Principal Investigator on the trial said:

“We are encouraged to see reductions in left ventricular volume measures in the CAP-1002 treated patients, an important indicator of reverse remodeling of the heart. These findings support the biological activity of CAP-1002.”

Capricor still has a clinical trial using CAP-1002 to treat boys and young men developing heart failure due to Duchenne Muscular Dystrophy (DMD).

Lithium gives up its mood stabilizing secrets

As far back as the late 1800s, doctors have recognized that lithium can help people with mood disorders. For decades, this inexpensive drug has been an effective first line of treatment for bipolar disorder, a condition that causes extreme mood swings. And yet, scientists have never had a good handle on how it works. That is, until this week.

evan snyder

Evan Snyder

Reporting in the Proceedings of the National Academy of Sciences (PNAS), a research team at Sanford Burnham Prebys Medical Discovery Institute have identified the molecular basis of the lithium’s benefit to bipolar patients.  Team lead Dr. Evan Snyder explained in a press release why his group’s discovery is so important for patients:

“Lithium has been used to treat bipolar disorder for generations, but up until now our lack of knowledge about why the therapy does or does not work for a particular patient led to unnecessary dosing and delayed finding an effective treatment. Further, its side effects are intolerable for many patients, limiting its use and creating an urgent need for more targeted drugs with minimal risks.”

The study, funded in part by CIRM, attempted to understand lithium’s beneficial effects by comparing cells from patient who respond to those who don’t (only about a third of patients are responders). Induced pluripotent stem cells (iPSCs) were generated from both groups of patients and then the cells were specialized into nerve cells that play a role in bipolar disorder. The team took an unbiased approach by looking for differences in proteins between the two sets of cells.

The team zeroed in on a protein called CRMP2 that was much less functional in the cells from the lithium-responsive patients. When lithium was added to these cells the disruption in CRMP2’s activity was fixed. Now that the team has identified the molecular location of lithium’s effects, they can now search for new drugs that do the same thing more effectively and with fewer side effects.

The stem cell: a biological calculator?

math

Can stem cells do math?

Stem cells are pretty amazing critters but can they do math? The answer appears to be yes according to a fascinating study published this week in PNAS Proceedings of the National Academy of Sciences.

Stem cells, like all cells, process information from the outside through different receptors that stick out from the cells’ outer membranes like a satellite TV dish. Protein growth factors bind those receptors which trigger a domino effect of protein activity inside the cell, called cell signaling, that transfers the initial receptor signal from one protein to another. Ultimately that cascade leads to the accumulation of specific proteins in the nucleus where they either turn on or off specific genes.

Intuition would tell you that the amount of gene activity in response to the cell signaling should correspond to the amount of protein that gets into the nucleus. And that’s been the prevailing view of scientists. But the current study by a Caltech research team debunks this idea. Using real-time video microscopy filming, the team captured cell signaling in individual cells; in this case they used an immature muscle cell called a myoblast.

goentoro20170508

Behavior of cells over time after they have received a Tgf-beta signal. The brightness of the nuclei (circled in red) indicates how much Smad protein is present. This brightness varies from cell to cell, but the ratio of brightness after the signal to before the signal is about the same. Image: Goentoro lab, CalTech.

To their surprise the same amount of growth factor given to different myoblasts cells led to the accumulation of very different amounts of a protein called Smad3 in the cells’ nuclei, as much as a 40-fold difference across the cells. But after some number crunching, they discovered that dividing the amount of Smad3 after growth factor stimulation by the Smad3 amount before growth stimulation was similar in all the cells.

As team lead Dr. Lea Goentoro mentions in a press release, this result has some very important implications for studying human disease:

“Prior to this work, researchers trying to characterize the properties of a tumor might take a slice from it and measure the total amount of Smad in cells. Our results show that to understand these cells one must instead measure the change in Smad over time.”

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.

klassen

jCyte co-founder Dr. Henry Klassen

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

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

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

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

FDA

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

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

Paul Bresge

jCyte CEO Paul Bresge

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

 

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

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

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

 

 

Stem cell stories that caught our eye: spinal cord injury trial keeps pace; SMART cells make cartilage and drugs

CIRM-funded spinal cord injury trial keeping a steady pace

Taking an idea for a stem cell treatment and developing it into a Food and Drug Administration-approved cell therapy is like running the Boston Marathon because it requires incremental progress rather than a quick sprint. Asterias Biotherapeutics continues to keep a steady pace and to hit the proper milestones in its race to develop a stem cell-based treatment for acute spinal cord injury.


Just this week in fact, the company announced an important safety milestone for its CIRM-funded SciStar clinical trial. This trial is testing the safety and effectiveness of AST-OPC1, a human embryonic stem cell-derived cell therapy that aims to regenerate some of the lost movement and feeling resulting from spinal cord injuries to the neck.

Periodically, an independent safety review board called the Data Monitoring Committee (DMC) reviews the clinical trial data to make sure the treatment is safe in patients. That’s exactly what the DMC concluded as its latest review. They recommended that treatments with 10 and 20 million cell doses should continue as planned with newly enrolled clinical trial participants.

About a month ago, Asterias reported that six of the six participants who had received a 10 million cell dose – which is transplanted directly into the spinal cord at the site of injury – have shown improvement in arm, hand and finger function nine months after the treatment. These outcomes are better than what would be expected by spontaneous recovery often observed in patients without stem cell treatment. So, we’re hopeful for further good news later this year when Asterias expects to provide more safety and efficacy data on participants given the 10 million cell dose as well as the 20 million cell dose.

It’s a two-fer: SMART cells that make cartilage and release anti-inflammation drug
“It’s a floor wax!”….“No, it’s a dessert topping!”
“Hey, hey calm down you two. New Shimmer is a floor wax and a dessert topping!”

Those are a few lines from the classic Saturday Night Live skit that I was reminded of when reading about research published yesterday in Stem Cell Reports. The clever study generated stem cells that not only specialize into cartilage tissue that could help repair arthritic joints but the cells also act as a drug dispenser that triggers the release of a protein that dampens inflammation.

Using CRISPR technology, a team of researchers led by Farshid Guilak, PhD, at Washington University School of Medicine in St. Louis, rewired stem cells’ genetic circuits to produce an anti-inflammatory arthritis drug when the cells encounter inflammation. The technique eventually could act as a vaccine for arthritis and other chronic conditions. Image: ELLA MARUSHCHENKO

The cells were devised by a research team at Washington University School of Medicine in St. Louis. They started out with skin cells collected from the tails of mice. Using the induced pluripotent stem cell technique, the skin cells were reprogrammed into an embryonic stem cell-like state. Then came the ingenious steps. The team used the CRISPR gene-editing method to create a negative feedback loop in the cells’ inflammation response. They removed a gene that is activated by the potent inflammatory protein, TNF-alpha and replaced it with a gene that blocks TNF-alpha. Analogous experiments were carried out with another protein called IL-1.

Rheumatoid arthritis often affects the small joints causing painful swelling and disfigurement. Image: Wikipedia

Now, TNF-alpha plays a key role in triggering inflammation in arthritic joints. But this engineered cell, in the presence of TNF-alpha, activates the production of a protein that inhibits the actions of TNF-alpha. Then the team converted these stem cells into cartilage tissue and they went on to show that the cartilage was indeed resistant to inflammation. Pretty smart, huh? In fact, the researchers called them SMART cells for “Stem cells Modified for Autonomous Regenerative Therapy.” First author Dr. Jonathan Brunger summed up the approach succinctly in a press release:

“We hijacked an inflammatory pathway to create cells that produced a protective drug.”

This type of targeted treatment of arthritis would have a huge advantage over current anti-TNF-alpha therapies. Arthritis drugs like Enbrel, Humira and Remicade are very effective but they block the immune response throughout the body which carries an increased risk for serious infections and even cancer.

The team is now testing the cells in animal models of rheumatoid arthritis as well as other inflammation disorders. Those results will be important to determine whether or not this approach can work in a living animal. But senior Dr. Farshid Guilak also has an eye on future applications of SMART cells:

“We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, it’s possible we could make stem cells that would sense glucose and turn on insulin in response. We are using pluripotent stem cells, so we can make them into any cell type, and with CRISPR, we can remove or insert genes that have the potential to treat many types of disorders.”

Capricor reports positive results on CIRM-funded stem cell trial for Duchenne Muscular Dystrophy

Capricor Therapeutics, a Los Angeles-based company, published an update about its CIRM-funded clinical trial for patients with Duchenne muscular dystrophy (DMD), a devastating degenerative muscle disease that significantly reduces life expectancy.

The company reported positive results from their Phase I/II HOPE trial that’s testing the safety of their cardiosphere stem cell-based therapy called CAP-1002. The trial had 25 patients, 13 of which received the cells and 12 who received normal treatment. No serious adverse effects were observed suggesting that the treatment is “generally safe” thus far.

Patients given a single dose of CAP-1002 showed improvements “in certain measures of cardiac and upper limb function” after six months. They also experienced a reduction of cardiac scar tissue and a thickening of the heart’s left ventricle wall, which is typically thinned in DMD patients.

Capricor shared more details on their six-month trial results in a webcast this week, and you can read about them in this blog by Rare Disease Report.

Leading cause of death for DMD patients

DMD is a severe form of muscular dystrophy caused by a recessive genetic mutation in the dystrophin gene on the X chromosome. Consequently, men are much more likely to get the disease than women. Symptoms of DMD start with muscle weakness as early as four years of age, which then leads to deterioration of both skeletal and heart muscle. Heart disease is the leading cause of death in DMD patients – a fact that Capricor hopes to change with its clinical trial.

Capricor’s CEO, Dr. Linda Marbán, commented in a press release that the trial’s results support the findings of other researchers.

“These initial positive clinical results build upon a large body of preclinical data which illustrate CAP-1002’s potential to broadly improve the condition of those afflicted by DMD, as they show that cardiosphere-derived cells exert salutary effects on cardiac and skeletal muscle.”

Also quoted in the press release was Pat Furlong, DMD patient advocate and CEO of Parent Project Muscular Dystrophy.

Pat Furlong

“I’m excited to see these data, especially given the advanced nature of the patients in the HOPE trial. It is also gratifying to see the field of cell therapy making progress after more than two decades in development. It is our hope that CAP-1002 will have broad potential to improve the lives of patients with Duchenne muscular dystrophy.”

Pat recently spoke at the 2nd Annual CIRM Alpha Stem Cell Clinics meeting about her heartbreaking experience of losing two sons to DMD, both at a very young age. You can watch her speech below. We also featured her story and her inspiring efforts to promote DMD awareness in our 2016 Annual Report.

What to HOPE for next?

The trial is a year-long study and Capricor will report 12-month results at the end of 2017. In the meantime, Dr. Marbán and her team have plans to talk with the US Food and Drug Administration (FDA) about the regulatory options for getting CAP-1002 approved and on the market for DMD patients. She explained,

Linda Marban, CEO of Capricor Therapeutics

“We have submitted an FDA meeting request to discuss these results as well as next steps in our development of CAP-1002 for Duchenne muscular dystrophy, which includes our plan to begin a clinical trial of intravenously-administered CAP-1002 in the latter half of this year. We believe the interim HOPE results may enable us to pursue one of the FDA’s Expedited Programs for Serious Conditions, and we will apply for either or both of the Breakthrough Therapy and Regenerative Medicine Advanced Therapy (RMAT) designations for CAP-1002.”


Related Links:

Stem Cell Patient Advocates, Scientists and Doctors Unite Around a Common Cause

Some phrases just bring a smile to your face: “It’s a girl/boy”, “Congratulations, you got the job”, and “Another beer sir?” (or maybe that last one is just me). One other phrase that makes me smile is “packed house”. That’s why I was smiling so much at our Patient Advocate Event at UC San Diego last week. The room was jammed with around 150 patients and patient advocates who had come to hear about the progress being made in stem cell research.

Jonathan Thomas, Chair of the CIRM governing Board, kicked off the event with a quick run-through of our research, focusing on our clinical trials. As we have now funded 29 clinical trials, it really was a quick run-through, but JT did focus on a couple of remarkable stories of cures for patients suffering from Severe Combined Immunodeficiency (SCID) and Chronic Granulomatous Disease.

His message was simple. We have come a long way, but we still have a long way to go to fulfill our mission of accelerating stem cell treatments to patients with unmet medical needs. We have a target of 40 new clinical trials by 2020 and JT stressed our determination to do everything we can to reach that goal.

David Higgins, Parkinson’s Disease Advocate and CIRM Board Member (Credit Cory Kozlovich, UCSD)

Next up was David Higgins, who has a unique perspective. David is a renowned scientist, he’s also the Patient Advocate for Parkinson’s disease on the CIRM Board, and he has Parkinson’s disease. David gave a heartfelt presentation on the changing role of the patient and their growing impact on health and science.

In the old days, David said, the patient was merely the recipient of whatever treatment a doctor determined was appropriate. Today, that relationship is much more like a partnership, with physician and patient working together to determine the best approach.

He said CIRM tries to live up to that model by engaging the voice of the patient and patient advocate at every stage of the approval process, from shaping concepts to assessing the scientific merits of a project and deciding whether to fund it, and then doing everything we can to help it succeed.

He said California can serve as the model, but that patients need to make their voices heard at the national level too, particularly in light of the proposed huge budget cuts for the National Institutes of Health.

Dr. Jennifer Braswell. (Credit Cory Kozlovich, UCSD)

U.C. San Diego’s Dr. Jennifer Braswell gave some great advice on clinical trials, focusing on learning how to tell a good trial from a questionable one, and the questions patients need to ask before agreeing to be part of one.

She said it has to:

  • Be at a highly regarded medical center
  • Be based on strong pre-clinical evidence
  • Involved well-informed and compassionate physicians and nurses
  • Acknowledge that it carries some risk.

“You all know that if it sounds too good to be true, it probably is. If someone says a clinical trial carries no risk that’s a red flag, you know that’s not true. There is risk. Good researchers work hard to reduce the risk as much as possible, but you cannot eliminate it completely.”

She said even sites such as www.clinicaltrials.gov – a list of all the clinical trials registered with the National Institutes of Health – have to be approached cautiously and that you should talk to your own physican before signing up for anything.

Finally, UC San Diego’s Dr. Catriona Jamieson talked about her research into blood cancers, and how her work would not have been possible without the support of CIRM. She also highlighted the growing number of trials being carried out at through the CIRM Alpha Stem Cell Clinic Network, which helps scientists and researchers share knowledge and resources, enabling them to improve the quality of the care they provide patients.

The audience asked the panelists some great questions about the need for;

  • A national patient database to make it easier to recruit people for clinical trials
  • For researchers to create a way of letting people know if they didn’t get into a clinical trial so the patients wouldn’t get their hopes up
  • For greater public education about physicians or clinics offering unproven therapies

Adrienne Shapiro, an advocate for sickle cell disease patients, asks a question at Thursday’s stem cell meeting in La Jolla. (Bradley J. Fikes)

The meeting showed the tremendous public interest in stem cell research, and the desire to move it ahead even faster.

This was the first of a series of free public events we are holding around California this year. Next up, Los Angeles. More details of that shortly.

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

retinitis pigmentosas_1

How retinitis pigmentosa destroys vision

Studies show that Americans fear losing their vision more than any other sense, such as hearing or speech, and almost as much as they fear cancer, Alzheimer’s and HIV/AIDS. That’s not too surprising. Our eyes are our connection to the world around us. Sever that connection, and the world is a very different place.

For people with retinitis pigmentosa (RP), the leading cause of inherited blindness in the world, that connection is slowly destroyed over many years. The disease eats away at the cells in the eye that sense light, so the world of people with RP steadily becomes darker and darker, until the light goes out completely. It often strikes people in their teens, and many are blind by the time they are 40.

There are no treatments. No cures. At least not yet. But now there is a glimmer of hope as a new clinical trial using stem cells – and funded by CIRM – gets underway.

klassenWe have talked about this project before. It’s run by UC Irvine’s Dr. Henry Klassen and his team at jCyte. In the first phase of their clinical trial they tested their treatment on a small group of patients with RP, to try and ensure that their approach was safe. It was. But it was a lot more than that. For people like Rosie Barrero, the treatment seems to have helped restore some of their vision. You can hear Rosie talk about that in our recent video.

Now the same treatment that helped Rosie, is going to be tested in a much larger group of people, as jCyte starts recruiting 70 patients for this new study.

In a news release announcing the start of the Phase 2 trial, Henry Klassen said this was an exciting moment:

“We are encouraged by the therapy’s excellent safety track record in early trials and hope to build on those results. Right now, there are no effective treatments for retinitis pigmentosa. People must find ways to adapt to their vision loss. With CIRM’s support, we hope to change that.”

The treatment involves using retinal progenitor cells, the kind destroyed by the disease. These are injected into the back of the eye where they release factors which the researchers hope will help rescue some of the diseased cells and regenerate some replacement ones.

Paul Bresge, CEO of jCyte, says one of the lovely things about this approach, is its simplicity:

“Because no surgery is required, the therapy can be easily administered. The entire procedure takes minutes.”

Not everyone will get the retinal progenitor cells, at least not to begin with. One group of patients will get an injection of the cells into their worst-sighted eye. The other group will get a sham injection with no cells. This will allow researchers to compare the two groups and determine if any improvements in vision are due to the treatment or a placebo effect.

The good news is that after one year of follow-up, the group that got the sham injection will also be able to get an injection of the real cells, so that if the therapy is effective they too may be able to benefit from it.

Rosie BarreroWhen we talked to Rosie Barrero about the impact the treatment had on her, she said it was like watching the world slowly come into focus after years of not being able to see anything.

“My dream was to see my kids. I always saw them with my heart, but now I can see them with my eyes. Seeing their faces, it’s truly a miracle.”

We are hoping this Phase 2 clinical trial gives others a chance to experience similar miracles.


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Listening is fine. Action is better. Why patients want more than just a chance to have their say.

FDA

Type in the phrase “the power of the patient voice” in any online search engine and you’ll generate thousands of articles and posts about the importance of listening to what patients have to say. The articles are on websites run by a diverse group from patients and researchers, to advocacy organizations and pharmaceutical companies. Everyone it seems recognizes the importance of listening to what the patient says. Even the Food and Drug Administration (FDA) has gotten in on the act. But what isn’t as clear is does all that talking and listening lead to any action?

In the last few years the FDA launched its ‘Patient-Focused Drug Development Initiative’, a series of public meetings where FDA officials invited patients and patient advocates to a public meeting to offer their perspectives on their condition and the available therapies. Each meeting focused on a different disease or condition, 20 in all, ranging from Parkinson’s and breast cancer to Huntington’s and sickle cell disease.

The meetings followed a standard format. Patients and patient advocates were invited to talk about the disease in question and its impact on their life, and then to comment on the available treatments and what they would like to see happen that could make their life better.

The FDA then gathered all those observations and comments, including some submitted online, and put them together in a report. Here’s where you can find all 20 FDA Voice of the Patient reports.  The reports all end with a similar concluding paragraph. Here’s what the conclusion for the Parkinson’s patient report said:

“The insight provided during this meeting will aid in FDA’s understanding of what patients truly value in a treatment and inform the agency’s evaluation of the benefits and risk of future treatments for Parkinson’s disease patients.”

And now what? That’s the question many patients and patient advocates are asking. I spoke with several people who were involved in these meetings and all came away feeling that the FDA commissioners who held the hearings were sincere and caring. But none believe it has made any difference, that it has led to any changes in policy.

For obvious reasons none of those I spoke to wanted to be identified. They don’t want to do anything that could in any way jeopardize a potential treatment for their condition. But many felt the hearings were just window dressing, that the FDA held them because it was required by Congress to do so. The Ageny, however, is not required to act on the conclusions or make any changes based on the hearings. And that certainly seems to be what’s happened.

Producing a report is fine. But if that report then gets put on a shelf and ignored what is the value of it? Patients and patient advocates want their voices to be heard. But more importantly they want what they say to lead to some action, to have some positive outcome. Right now they are wondering if they were invited to speak, but no one was really listening.

 

 

A life-threatening childhood disease and the CIRM-funded team seeking a stem cell cure featured in new video

“My hope for Brooke is she can one day look back and we have to remind her of the disease she once had.”

That’s Clay Emerson’s biggest hope for his young daughter Brooke, who has cystinosis, a life-threatening genetic disease that appears by the age of two and over time causes damage to many organs, especially the kidneys and eyes but also the liver, muscle, brain, pancreas and other tissues. The Emersons and other families affected by the disease are featured in a recent video produced by the Cystinosis Research Foundation.

I doubt many can watch the seven-minute piece without getting a lump in their throat or watery eyes. One of many heart wrenching scene shows Brooke’s mother, Jill Emerson, preparing a day’s worth of medicine that she administers through a tube connected to Brook’s stomach.

“Brooke takes about 20 doses of medication a day and that’s throughout the 24hr period in a day. The poor kid hasn’t had a full night’s sleep ever in her entire life because I have to wake her up to take her life-saving medicine.”

Jill Emerson prepares a day’s worth of medicine for her daughter Brooke. Unfortunately, the treatments only slow the progression of cystinosis but don’t cure it. (Video Still: Cystinosis Research Foundation)

But these treatments only slow down the progression of this incurable disease. Even perfect compliance with taking the medicine doesn’t stop severe complications of the disease including kidney failure, diabetes, muscle weakness, and difficulty swallowing just to name a few. Cystinosis also shorten life spans. Natalie, the video’s narrator, a young woman with cystinosis wonders how much time she has left:

“There are people in their 20s who have recently died from cystinosis. I am 25 years old and I often think about how long I have to live. I’m praying for a cure for all of us.”

Her prayers may be answered in the form of a stem cell gene therapy treatment. UCSD researcher Dr. Stephanie Cherqui, who is also featured in the video, received $5 million in CIRM funding to bring her team’s therapy to clinical trials in people.

At a cellular level, cystinosis is caused by mutations in a gene called CTNS which lead to an accumulation of the amino acid cysteine. The excess cysteine eventually forms crystals causing devastating damage to cells throughout the body. Cherqui’s treatment strategy is to take blood stem cells from affected individuals, insert a good copy of the CTNS gene using genome editing into the cells’ DNA, and then transplant the cells back into the patient.

Cystinosis_Cherqui

Dr. Stephanie Cherqui and her team are working hard to bring a stem cell gene therapy treatment for cystinosis to clinical trials. (Video Still: Cystinosis Research Foundation)

Her team has preliminary evidence that the strategy works in mice. Now, they will use the CIRM grant to complete these pre-clinical studies and prepare the genetically engineered blood stem cells for use in patients. These steps are necessary to get the green light from the Food and Drug Administration (FDA) to begin clinical trials, hopefully some time this year.

Cherqui says that if all goes well, the treatment approach may have benefits beyond cystinosis:

“If we can bring this to the finish line, we can then show the way to maybe hundreds, maybe thousands of other genetic diseases. So this could be a real benefit to mankind.”