When the voters of California approved Proposition 14 last November (thanks folks) they gave us $5.5 billion to continue the work we started way back in 2014. It’s a great honor, and a great responsibility.
It’s also a great opportunity to look at what we do and how we do it and try to come up with even better ways of funding groundbreaking research and helping create a new generation of researchers.
In addition to improving on what we already do, Prop 14 introduced some new elements, some new goals for us to add to the mix, and we are in the process of fleshing out how we can best do that.
Because of all these changes we decided it would be a good idea to hold a “Town Hall” meeting and let everyone know what these changes are and how they may impact applications for funding.
The Town Hall, on Tuesday June 29, was a great success with almost 200 participants. But we know that not everyone who wanted to attend could, so here’s the video of the event, and below that are the questions that were posed by people during the meeting, and the answers to those questions.
Having seen the video we would be eternally grateful if you could respond to a short online survey, to help us get a better idea of your research and education needs and to be better able to serve you and identify potential areas of opportunity for CIRM. Here’s a link to that survey: https://www.surveymonkey.com/r/VQMYPDL
We know that there may be issues or questions that are not answered here, so feel free to send those to us at info@cirm.ca.gov and we will make sure you get an answer.
Are there any DISC funding opportunities specific to early-stage investigators?
DISC funding opportunities are open to all investigators. There aren’t any that are specific to junior investigators.
Are DISC funding opportunities available for early-mid career researchers based out of USA such as Australia?
Sorry, you have to be in California for us to fund your work.
Does tumor immunology/ cancer immunotherapy fall within the scope of the CIRM discovery grants?
Hi, when will reviews for DISC 2: CIRM Quest – Discovery Stage Research Projects (deadline March 2021) be available? Thanks!
Review summaries for the March 2021 Discovery submitted applications will be available by mid-August, with final board funding decisions at the August 24th Application Review Subcommittee Meeting
Has CIRM project made it to Phase III or product launch with FDA approval? What is CIRM strategy for start-up biotech companies?
CIRM funding supports non-profit academic grantees as well as companies of all sizes.
I am studying stem cells using mouse. Is my research eligible for the CIRM grants?
Yes it is.
Your programs more specifically into stem cell research would be willing to take patients that are not from California?
Yes, we have treated patients who are not in California. Some have come to California for treatment and others have been treated in other states in the US by companies that are based here in California.
Can you elaborate how the preview of the proposals works? Who reviews them and what are the criteria for full review?
The same GWG panel both previews and conducts the full review. The panel first looks through all the applications to identify what each reviewer believes represents the most likely to be impactful and meet the goals of the CIRM Discovery program. Those that are selected by any reviewer moves forward to the next full review step.
If you meet your milestones-How likely is it that a DISC recipient gets a TRAN award?
The milestones are geared toward preparation of the TRAN stage. However, this is a different application and review that is not guaranteed to result in funding.
Regarding Manufacturing Public Private partnerships – What specific activities is CIRM thinking about enabling these partnerships? For example, are out of state for profit commercial entities able to conduct manufacturing at CA based manufacturing centers even though the clinical program may be primarily based out of CA? If so, what percent of the total program budget must be expended in CA? How will CIRM enable GMP manufacturing centers interact with commercial entities?
We are in the early stages of developing this concept with continued input from various stakeholders. The preliminary vision is to build a network of academic GMP manufacturing centers and industry partners to support the manufacturing needs of CIRM-funded projects in California.
We are in the process of widely distributing a summary of the manufacturing workshop. Here’s a link to it:
If a center is interested in being a sharing lab or competency hub with CIRM, how would they go about it?
CIRM will be soliciting applications for Shared Labs/Competency hubs in potential future RFAs. The survey asks several questions asking for feedback on these concepts so it would really help us if you could complete the survey.
Would preclinical development of stem cell secretome-derived protein therapies for rare neuromuscular diseases and ultimately, age-related muscle wasting be eligible for CIRM TRAN1 funding? The goal is to complete IND-enabling studies for a protein-based therapy that enhances tissue regeneration to treat a rare degenerative disease. the screening to identify the stem-cell secreted proteins to develop as therapeutics is done by in vitro screening with aged/diseased primary human progenitor cells to identify candidates that enhance their differentiation . In vivo the protein therapeutic signals to several cell types , including precursor cells to improve tissue homeostasis.
I would suggest reaching out to our Translation team to discuss the details as it will depend on several factors. You can email the team at translational@cirm.ca.gov
All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future.Today we feature a rare treat, an interview with Moderna’s Dr. Derrick Rossi.
Moderna co-founder Dr. Derrick Rossi
It’s not often you get a chance to sit down with one of the key figures in the fight against the coronavirus and get to pick his brain about the best ways to beat it. We were fortunate enough to do that on Wednesday, talking to Dr. Derrick Rossi, the co-founder of Moderna, about the vaccine his company has developed.
CIRM’s President and CEO, Dr. Maria Millan, was able to chat to Dr. Rossi for one hour about his background (he got support from CIRM in his early post-doctoral research at Stanford) and how he and his colleagues were able to develop the COVID-19 vaccine, how the vaccine works, how effective it is, how it performs against new variations of the virus.
He also told us what he would have become if this science job hadn’t worked out.
All in all it was a fascinating conversation with someone whose work is offering a sense of hope for millions of people around the world.
If you missed it first time around you can watch it here.
What are the latest advances in stem cell research targeting cancer? Can stem cells help people battling COVID-19 or even help develop a vaccine to stop the virus? What are researchers and the scientific community doing to help address the unmet medical needs of underserved communities? Those are just a few of the topics being discussed at the Annual CIRM Alpha Stem Cell Clinic Network Symposium on Thursday, October 8th from 9am to 1.30pm PDT.
Like pretty nearly everything these days the symposium is going to be a virtual event, so you can watch it from the comfort of your own home on a phone or laptop. And it’s free.
The CIRM Alpha Clinics are a network of leading medical centers here in California. They specialize in delivering stem cell and gene therapies to patients. So, while many conferences look at the promise of stem cell therapies, here we deal with the reality; what’s in the clinic, what’s working, what do we need to do to help get these therapies to patients in need?
It’s a relatively short meeting, with short presentations, but that doesn’t mean it will be short on content. Some of the best stem cell researchers in the U.S. are taking part so you’ll learn an awful lot in a short time.
We’ll hear what’s being done to find therapies for
Rare diseases that affect children
Type 1 diabetes
HIV/AIDS
Glioblastoma
Multiple myeloma
We’ll discuss how to create a patient navigation system that can address social and economic determinants that impact patient participation? And we’ll look at ways that the Alpha Clinic Network can partner with community care givers around California to increase patient access to the latest therapies.
It’s going to be a fascinating day. And did I mention it’s free!
All you have to do is go to this Eventbrite page to register.
And feel free to share this with your family, friends or anyone you think might be interested.
Every so often you hear a story and your first reaction is “oh, I have to share this with someone, anyone, everyone.” That’s what happened to me the other day.
I was talking with Kristin MacDonald, an amazing woman, a fierce patient advocate and someone who took part in a CIRM-funded clinical trial to treat retinitis pigmentosa (RP). The disease had destroyed Kristin’s vision and she was hoping the therapy, pioneered by jCyte, would help her. Kristin, being a bit of a pioneer herself, was the first person to test the therapy in the U.S.
Anyway, Kristin was doing a Zoom presentation and wanted to look her best so she asked a friend to come over and do her hair and makeup. The woman she asked, was Rosie Barrero, another patient in that RP clinical trial. Not so very long ago Rosie was legally blind. Now, here she was helping do her friend’s hair and makeup. And doing it beautifully too.
That’s when you know the treatment works. At least for Rosie.
There are many other stories to be heard – from patients and patient advocates, from researchers who develop therapies to the doctors who deliver them. – at our CIRM 2020 Grantee Meeting on next Monday September 14th Tuesday & September 15th.
It’s two full days of presentations and discussions on everything from heart disease and cancer, to COVID-19, Alzheimer’s, Parkinson’s and spina bifida. Here’s a link to the Eventbrite page where you can find out more about the event and also register to be part of it.
Like pretty much everything these days it’s a virtual event so you’ll be able to join in from the comfort of your kitchen, living room, even the backyard.
And it’s free!
You can join us for all two days or just one session on one day. The choice is yours. And feel free to tell your friends or anyone else you think might be interested.
Way back in 2013, the CIRM Board invested $32 million in a project to create an iPSC Bank. The goal was simple; to collect tissue samples from people who have different diseases, turn those samples into high quality stem cell lines – the kind known as induced pluripotent stem cells (iPSC) – and create a facility where those lines can be stored and distributed to researchers who need them.
Fast forward almost seven years and that idea has now become the largest public iPSC bank in the world. The story of how that happened is the subject of a great article (by CIRM’s Dr. Stephen Lin) in the journal Science Direct.
Dr. Stephen Lin
In 2013 there was a real need for the bank. Scientists around the world were doing important research but many were creating the cells they used for that research in different ways. That made it hard to compare one study to another and come up with any kind of consistent finding. The iPSC Bank was designed to change that by creating one source for high quality cells, collected, processed and stored under a single, consistent method.
Tissue samples – either blood or skin – were collected from thousands of individuals around California. Each donor underwent a thorough consent process – including being shown a detailed brochure – to explain what iPS cells are and how the research would be done.
The diseases to be studied through this bank include:
Age-Related Macular Degeneration (AMD)
Alzheimer’s disease
Autism Spectrum Disorder (ASD)
Cardiomyopathies (heart conditions)
Cerebral Palsy
Diabetic Retinopathy
Epilepsy
Fatty Liver diseases
Hepatitis C (HCV)
Intellectual Disabilities
Primary Open Angle Glaucoma
Pulmonary Fibrosis
The samples were screened to make sure they were safe – for example the blood was tested for HBV and HIV – and then underwent rigorous quality control testing to make sure they met the highest standards.
Once approved the samples were then turned into iPSCs at a special facility at the Buck Institute in Novato and those lines were then made available to researchers around the world, both for-profit and non-profit entities.
Scientists are now able to use these cells for a wide variety of uses including disease modeling, drug discovery, drug development, and transplant studies in animal research models. It gives them a greater ability to study how a disease develops and progresses and to help discover and test new drugs or other therapies
The Bank, which is now run by FUJIFILM Cellular Dynamics, has become a powerful resource for studying genetic variation between individuals, helping scientists understand how disease and treatment vary in a diverse population. Both CIRM and Fuji Film are committed to making even more improvements and additions to the collection in the future to ensure this is a vital resource for researchers for years to come.
Making sure patients get the treatment they need and not a “snake oil” substitute
We are at a turning point in regenerative medicine as the first wave of treatments have obtained FDA approval. But at the same time as we see the advance of scientifically rigorous research and regulated products we are also witnessing the continued proliferation of “unproven treatments.” This dueling environment can be overwhelming and distracting to individuals and families trying to manage life-threatening diseases.
How does a patient navigate this environment and get trusted and reliable information to help sort through their options?
CIRM teamed up with the CURA Foundation to organize a roundtable discussion intended to answer this question. The conversation included thought leaders involved in patient advocacy, therapy research and development, public policy and research funding. The roundtable was divided into three segments designed to discuss:
Examples of state-of-the-art patient navigation systems,
Policy, research and infrastructure needs required to expand navigation systems, and
Communication needs for engaging patients and the broader community.
Examples of Navigation Systems:
This session was framed around the observation that patients often do not get the best medicines or treatments available for their condition. For example, in the area of cancer care there is evidence that the top 25% of cancers are not being treated optimally. Historic barriers to optimal treatment include cost pressures that may block access to treatments, lack of knowledge about the available treatments or the absence of experts in the location where the patient is being treated. Much of the session focused on how these barriers are being overcome by partnerships between health care provides, employers and patients.
For example, new technologies such as DNA sequencing and other cell-based markers enable better diagnosis of a patient’s underlying disease. This information can be collected by a community hospital and shared with experts who work with the treating doctor to consider the best options for the patient. If patients need to access a specialty center for treatment, there are new models for the delivery of such care. Emphasis is placed on building a relationship with the patient and their family by surrounding them with a team that can address any questions that arise. The model of patient-centered care is being embraced by employers who are purchasing suites of services for their employees.
Patient advocacy groups have also supported efforts to get the best information about the patients’ underlying disease. Advocacy organizations have been building tools to connect patients with researchers with the aim of allowing secure and responsible sharing of medical information to drive the patient-centered development of new treatments. In a related initiative, the American Society of Hematology is creating a data hub for clinical trials for sickle cell disease. Collectively, these efforts are designed to accelerate new treatments by allowing critical data to be shared among researchers.
Essential Policy Infrastructure for Regenerative Medicine:
Session two dovetailed nicely with first discussion. There was continued emphasis on the need for additional evidence (data) to demonstrate that regenerative medicine treatments are having a significant effect on the patient’s disease. Various speakers echoed the need for patients in clinical trials to work with researchers to determine the benefits of treatments. Success stories with gene therapies in blood diseases were cited as proof of concept where treatments being evaluated in clinical trials are demonstrating a significant and sustained impact on diseases. Evidence of benefit is needed by both regulatory bodies that approve the treatments, such as the FDA, and by public and private payers / insurers that pay for treatments and patients that need to know the best option for their particular disease.
In addition, various speakers cited the continued proliferation of “unproven treatments” being marketed by for-profit centers. There was broad concern that the promotion of treatment where there is no evidence of effectiveness will mislead some patients and potentially harm the scientifically rigorous development of new treatments. Particularly for “stem cell” treatments, there was a desire to develop evaluation criteria that are clear and transparent to allow legitimate treatments to be distinguished from those with no evidence of effectiveness. One participant suggested there be a scorecard approach where specific treatments could be rated against specific indicators of safety, medical benefit and value in relation to alternative treatments. The idea would be to make this information widely available to patients, medical providers and the public to inform everything from medical decision making to advertising.
Communicating the Vision
The final session considered communication needs for the field of regenerative medicine. Patients and patient advocacy organizations described how they are using social media and other networking tools to share information and experiences in navigating their treatment options. Patient advocacy groups also described the challenges from providers of unproven treatments. In one case, a for profit “pop up” clinic had used the group’s videos in an attempt to legitimize their unproven treatment.
There was general consensus among the panelists that the field of regenerative medicine needs “trusted intermediaries” who can evaluate claims and help patients distinguish between high quality research and “snake oil”. These intermediaries should have the capacity to compile the most reliable evidence and utilize it to determine what options are available to patients. In addition, there needs to be shared decision making model where patients have the opportunity to explore options in an unbiased environment so they may make the best decision based on their specific needs and values.
Creating this kind of Navigation System will not be easy but the alternative is unacceptable. Too many vulnerable patients are being taken advantage of by the growing number of “predatory clinics” hawking expensive therapies that are both unproven and unapproved. We owe it to these patients to create a simple way for them to identify what are the most promising therapies, ones that have the highest chance of being both safe and effective. The roundtable discussion marked a starting point, bringing together many of the key players in the field, highlighting the key issues and beginning to identify possible solutions.
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.
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:
Visual loss from damage to the retina
You could have a normal eye with damage to the area of the brain that controls the eye’s movement
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?
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.
Health Citizenship panel discussion at Partnering for Cures: L to R: Lucia Savage, Roni Zeiger, Claudia Williams, Jennifer Mills, Kathy Hudson, Beth Meagher
One of the buzz phrases in healthcare today is “patient engagement”. It seems that you can’t go to a medical or scientific conference without coming across a panel discussion on the topic. A recent Partnering For Cures* event in San Francisco was no exception. But here the conversation took on a very different tone, one that challenged what the term meant and then said that if we are really serious about engaging patients, then doctors and drug companies need to change the way they think and operate.
That tone was set from the start of the discussion when moderator Claudia Williams said even the term “patient engagement” suggests that it is something “being imposed, or at least allowed, from the outside; by experts and doctors and those in charge.”
Williams quoted Erin Moore, the mother of a young boy with cystic fibrosis saying “No one is more engaged than the patient. I want the experts, the doctors, the pharmaceutical companies to be engaged.”
Need to train doctors
Dr. Roni Zeiger, the former Chief Health Strategist at Google, said doctors aren’t trained to truly listen to and engage with patients, and that has to change:
“I sometimes think of myself as a recovering paternal physician. When I listen to and learn from patients and families I am surprised, every time, at the breadth and depth of the conversations. All of the things that we, in the medical field, do from designing a waiting room to designing a clinical trial to deciding when and how to have a conversation, we bring a tremendous amount of assumptions to those. And those assumptions are often wrong. I think that on a daily basis we should be looking at the key work we do and ask are there assumptions here I should throw away and talk to those I serve and get their help in redesigning things in a way that makes more sense.”
Jennifer Mills, the Director of Patient Engagement (that phrase again) at biotech giant Genentech, said those mistakes are made by everyone in the field:
“The biggest assumption for me is thinking about patients with a capital P, as a homogeneous group, instead of realizing they are also individuals. We need to address them as a group and as individuals depending on the circumstances.”
Caregivers count too
For example as people get older and rely on a partner or spouse to take care of them it may be important to not just engage with the patient but also with the caregiver. And the needs for each of them may not be the same.
At that point the conversation turned to the use of data. Lucia Savage, the Chief Privacy and Regulatory Officer at Omada Health, said it is going to be increasingly important to give people control over their own medical data, and sometimes the medical data of others.
“Caregivers need access to healthcare records. For example, I can check my mom’s labs. If I message her doctors they can share that information with me. It’s great because it helps us help her lead an independent life as an 80 year old.”
Savage also pointed out that we need to be careful how we interpret data. She said she could go shopping and buy three extra-large bags of potato chips. On the face of it that doesn’t look good. But did she buy those chips for herself or her daughter’s soccer team. The data is the same. The implications are very different.
Partnership not patronizing
The discussion ended with an attempt to outline what being a good health citizen means. Just as citizenship involves both rights and responsibilities on the part of the individual and society, health citizenship too involves rights and responsibilities on the part of the individual and the biomedical research and health care world. Patients deserve to be treated as individuals who have a vested interest in their own health. They don’t need “experts” to talk down or patronize them or assume they know best.
Mills says she is seeing progress in this area:
“Companies are moving from assuming what patients need to asking what they need. We once assumed that if we were in the therapeutic area long enough we didn’t need to ask what patients need. I’m seeing that change.”
Deloitte Consulting’s Beth Meagher said we need to look beyond technology and focus on the people:
“Humility is going to be the killer app. The true innovators are really being humble and realizing that to have the kind of impact they are looking for, there is a need to work in a way they haven’t before. “
*Partnering for Cures is a project of Michael Milken’s FasterCures, whose goal is to save lives by speeding up and improving the medical research system.
During this second week of the Month of CIRM, we’ve been focusing on the people who are critical to accomplishing our mission to accelerate stem cell treatments to patients with unmet medical needs.
These folks include researchers, like Clive Svendsen and his team at Cedars-Sinai Medical Center who are working tirelessly to develop a stem cell therapy for ALS. My colleague Karen Ring, CIRM’s Social Media and Website Manager, featured Dr. Svendsen and his CIRM-funded clinical trial in Monday’s blog. And yesterday, in recognition of Stem Cell Awareness Day, Kevin McCormack, our Senior Director of Public Communications, blogged about the people within the stem cell community who have made, and continue to make, the day so special.
Today, in a new video, I highlight a brave young patient, Ronnie, and his parents who decided to participate in a CIRM-funded clinical trial run by St. Jude Children’s Research Hospital and UC San Francisco in an attempt to save Ronnie’s life from an often-fatal disease called severe combined immunodeficiency (SCID). This disorder, also known as bubble baby disease, leaves newborns without a functioning immune system which can turn a simple cold into a potentially deadly infection.
Watch this story’s happy ending in the video above.
This week in Washington DC a delegation from the stem cell advocacy group Texans for Cures is meeting with members of Congress from both parties. The focus of the meetings are three bills promoting “Right to Try” legislation. Supporters of the bills say they will empower patients battling terminal illness. Texans for Cures say, quite the contrary, that these laws will endanger patients. In this guest blog, Texans for Cures explain why they feel these laws are bad.
In 2014, the Goldwater Institute published a policy report titled, “Everyone Deserves the Right to Try: Empowering the Terminally Ill to Take Control of their Treatment.”[i] The report calls for states to pass “Right to Try” legislation as a means to reclaim patients’ medical autonomy and right to determine their own medical treatment.
This policy recommendation is built on the theory that the Food and Drug Administration (FDA) should not be able to restrict terminal patients’ access to potentially life-saving treatments so long as the treatment has been tested for basic safety. While this idea may seem immediately appealing, the policy undermines medical research in several ways that are harmful to the development of new treatments.
Texans for Cures opposes this legislation because it harms the sound development of treatments for future patients on the mere chance that it may provide relief to current patients that have received a terminal diagnosis. In short, Right to Try policies ignore the attendant risks and overemphasize the potential benefits.
“Right to Try” Model Legislation and State Enacted Variants
The Goldwater Institute’s policy report included model legislation for interested legislators, which it summed up as follows:
Simply stated, Right to Try allows a patient to access investigational medications that have passed basic safety tests without interference by the government when the following conditions are met:
The patient has been diagnosed with a terminal disease;
The patient has considered all available treatment options;
The patient’s doctor has recommended that the investigational drug, device, or biological product represents the patient’s best chance at survival;
The patient or the patient’s guardian has provided informed consent; and
The sponsoring company chooses to make the investigational drug available to patients outside the clinical trial.
Since the Goldwater Institute published this policy report in 2014, 33 states have enacted Right to Try laws.[ii] These laws contain minor variations from the model legislation, but each operates similarly to limit the FDA’s oversight roll.
Right to Try is Loosely Grounded in the Constitution and May Require Federal Action
Due to the fact that these laws may infringe on the FDA’s authority over drug development and distribution, the policy report attempts to ground Right to Try in one’s constitutional right to liberty. This constitutional underpinning is loose and is not firmly supported by Supreme Court precedent.[iii] With the constitutional basis of Right to Try resting on a weak foundation, it is important for Right to Try proponents to pass a complimentary Right to Try statute on the federal level in Congress.
There are three bills actively working through the Congressional process that would prohibit the FDA or any other federal agency from interfering with a patient’s Right to Try: H.R. 878 by Representative Biggs,[iv] H.R. 2368 by Representative Fitzpatrick,[v] and S. 204 by Senator Johnson.[vi] Each of these bills shares three common provisions, while H.R. 2368 has two additional provisions:
Common Provisions:
Prohibition on federal action
No liability
No use of outcomes
Provisions Unique to H.R. 2368:
Manufacturers are not required to make treatments available
Permits manufacturers to receive compensation or recover costs
All three of the federal bills would remove the FDA’s ability to intervene in state Right to Try programs. They also create a liability shield for any producer, manufacturer, distributor, prescriber, dispenser, possessor, or user participating in the program. And finally, each prohibits the use of outcomes from patients participating in Right to Try as a criteria for FDA review of the treatment. This means that harmed patients would have limited or no legal recourse, and the FDA may need another Act of Congress to grant them the authority to intervene in any programs that prove to be dangerous. However, it may be difficult to know if these programs are harming patients or not, because the bills do not provide any mechanism for tracking outcomes and using that information for oversight.
Each bill is drafted in a way that would remove FDA oversight authority and would allow states to proceed with Right to Try policies and grants states broad discretion to tailor these programs without federal oversight. However, H.R. 2368 contains two additional provisions that would compliment and potentially override state statute. First, the bill gives manufacturers the authority to deny patients access to investigational treatments, which is consistent with the Goldwater Institute’s model legislation. Second, the bill allows manufacturers to receive compensation or recover costs involved in making the drug available to patients. This second provision is particularly problematic in that it would allow manufacturers to charge patients for unproven treatments unless they were explicitly prohibited from doing so by state law.
How Right to Try Laws Structurally Harm the Research Process
Right to Try laws create a number of problematic incentives and penalties that would likely harm the long term development of new therapies. First and foremost, under Right to Try, patients will be able to bypass the clinical trial process, request investigational treatments, and pay the cost of the drug, rather than enter into a clinical trial. Given that clinical trials may involve the use of placebos, Texans for Cures is concerned that patients may choose to exercise Right to Try rather than participate in a clinical trial, because under Right to Try the patient avoids the possibility of receiving a placebo.
Additionally, there is no mechanism in the proposed bills for tracking outcomes of patients participating in Right to Try, and there is no mechanism for government intervention if Right to Try proves to be unreasonably risky.
Right to Try seeks to shield all participants from liability, meaning that patients who are harmed will have limited or no legal recourse, even if manufacturers or physicians are negligent. Furthermore, Right to Try laws typically allow manufacturers to recover the cost of manufacturing the treatment for participating patients, but cost is not defined. Does cost include the cost of research and development or is it exclusively the cost of creating that specific treatment? The ambiguity surrounding this term is a cause for concern, because companies may be tempted to use this ambiguity to cover a broader sets of costs than the authors intended.
Conclusion
Texans for Cures opposes this legislative effort because the program could potentially harm patients and, if it does, the law does not provide adequate safeguards or remedies. Additionally, the law does not require any monitoring of outcomes and is therefore unscientific in its approach to treatments that are currently undergoing clinical research.
The FDA is already working to ease the burdens associated with Expanded Access programs, which achieve the end that Right to Try desires: providing access to research drugs for terminal patients. The difference is that Expanded Access has additional safeguards and a mechanism for FDA intervention if treatment is found to be dangerous or harmful to the clinical trial process.
Finding scientifically sound treatments for patients in need is the primary concern of Texans for Cures. Texans for Cures sympathizes with, and its members have similarly experienced, the pain of losing loved ones. The hope and emotion involved in Right to Try laws is not to be taken lightly, but it is precisely because strong emotions can cloud our judgment that we, as a society, must approach the clinical trial process with a clear mental state. Texans for Cures believes that Right to Try will harm the long term development of new treatments and therefore asks for your help in fighting this legislative effort.
3 The Goldwater Institute’s sole source for constitutional grounding for this law comes from a concurrence by Justice Douglas in Doe v. Bolton, 410 U.S. 179, 218 (1973), where he noted that individuals have a “right to care for one’s health and person.” The Goldwater Institute appears to recognize the precarious footing of their model legislation, stating in their policy report, “Although the right of terminal patients to access investigational medications has not yet been recognized by the Supreme Court, it is consistent with and can be supported by existing precedent.”
The Stem Cellar 