A study published in the New England Journal of Medicine shows that an experimental form of stem cell and gene therapy has cured 48 of 50 children born with a deadly condition called ADA-SCID.
Children with ADA-SCID, (severe combined immunodeficiency due to adenosine deaminase deficiency) lack a key enzyme that is essential for a healthy, functioning immune system. As a result, even a simple infection could prove fatal to these children and, left untreated, most will die within the first two years of life.
In the study, part of which was supported by CIRM, researchers at the University of California Los Angeles (UCLA) and Great Ormond Street Hospital (GOSH) in London took some of the children’s own blood-forming stem cells and, in the lab, corrected the genetic mutation that causes ADA-SCID. They then returned those cells to the children. The hope was that over time the corrected stem cells would create a new blood supply and repair the immune system.
In the NEJM study the researchers reported outcomes for the children two and three years post treatment.
“Between all three clinical trials, 50 patients were treated, and the overall results were very encouraging,” said Dr. Don Kohn, a distinguished professor of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “All the patients are alive and well, and in more than 95% of them, the therapy appears to have corrected their underlying immune system problems.”
Two of the children did not respond to the therapy and both were returned to the current standard-of-care therapy. One subsequently underwent a bone marrow transplant. None of the children in the study experienced serious side-effects.
“This is encouraging news for all families affected by this rare but deadly condition,” says Maria T. Millan, MD, President and CEO of CIRM. “It’s also a testament to the power of persistence. Don Kohn has been working on developing this kind of therapy for 35 years. To see it paying off like this is a remarkable testament to his skill as a researcher and determination to help these patients.”
One of our favorite things to do at CIRM is deliver exciting news about CIRM projects. This usually entails discussion of recent discoveries that made headlines, or announcing the launch of a new CIRM-funded clinical trial …. tangible signs of progress towards addressing unmet medical needs through advances in stem technology.
But there are equally exciting signs of progress that are not always so obvious to the untrained eye- those that we are privileged to witness behind the scenes at CIRM. These efforts don’t always lead to a splashy news article or even to a scientific publication, but they nonetheless drive the evolution of new ideas and can help steer the field away from futile lines of investigation. Dozens of such projects are navigating uncharted waters by filling knowledge gaps, breaking down technical barriers, and working closely with regulatory agencies to define novel and safe paths to the clinic.
These efforts can remain “hidden” because they are in the intermediate stages of the long, arduous and expensive journey from “bench to beside”. For the pioneering projects that CIRM funds, this journey is unique and untrod, and can be fraught with false starts. But CIRM has developed tools to track the momentum of these programs and provide continuous support for those with the most promise. In so doing, we have watched projects evolve as they wend their way to the clinic. We wanted to share a few examples of how we do this with our readers, but first… a little background for our friends who are unfamiliar with the nuts and bolts of inventing new medicines.
A common metaphor for bringing scientific discoveries to market is a pipeline, which begins in a laboratory where a discovery occurs, and ends with government approval to commercialize a new medicine, after it is proven to be safe and effective. In between discovery and approval is a stage called “Translation”, where investigators develop ways to transition their “research level” processes to “clinically compatible” ones, which only utilize substances that are of certified quality for human use.
Investigators must also work out novel ways to manufacture the product at larger scale and transition the methods used for testing in animal models to those that can be implemented in human subjects.
A key milestone in Translation is the “preIND” (pre Investigational New Drug (IND) meeting, where an investigator presents data and plans to the US Food and Drug Administration (FDA) for feedback before next stage of development begins, the pivotal testing needed to show it is both safe and effective.
These “IND enabling studies” are rigorous but necessary to support an application for an IND and the initiation of clinical trials, beginning with phase 1 to assess safety in a small number of individuals, and phase 2, where an expanded group is evaluated to see if the therapy has any benefits for the patient. Phase 3 trials are studies of very large numbers of individuals to gain definitive evidence of safety and therapeutic effect, generally the last step before applying to the FDA for market approval. An image of the pipeline and the stages described are provided in our diagram below.
The pipeline can be notoriously long and tricky, with plenty of twists, turns, and unexpected obstacles along the way. Many more projects enter than emerge from this gauntlet, but as we see from these examples of ‘works in progress”, there is a lot of momentum building.
Caption for Graphic:This graphic shows the number of CIRM-funded projects and the stages they have progressed through multiple rounds of CIRM funding. For example, the topmost arrow shows that are about 19 projects at the translational stage of the pipeline that received earlier support through one of CIRM’s Discovery stage programs. Many of these efforts came out of our pre-2016 funding initiatives such as Early Translation, Basic Biology and New Faculty Awards. In another example, you can see that about 15 awards that were first funded by CIRM at the IND enabling stage have since progressed into a phase 1 or phase 2 clinical trials. While most of these efforts also originated in some of CIRM’s pre-2016 initiatives such as the Disease Team Awards, others have already progressed from CIRM’s newer programs that were launched as part of the “2.0” overhaul in 2016 (CLIN1).
The number of CIRM projects that have evolved and made their way down the pipeline with CIRM support is impressive, but it is clearly an under-representation, as there are other projects that have progressed outside of CIRM’s purview, which can make things trickier to verify.
We also track projects that have spun off or been licensed to commercial organizations, another very exciting form of “progression”. Perhaps those will contribute to another blog for another day! In the meantime, here are a just a few examples of some of the progressors that are depicted on the graphic.
Project: stem cell therapy to enhance bone healing in theelderly
– Currently funded stage: IND enabling development, CLIN1-11256 (Dr. Zhu, Ankasa Regenerative Therapeutics)
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.
It’s been a long time coming. Eighteen months to be precise. Which is a peculiarly long time for an Annual Report. The world is certainly a very different place today than when we started, and yet our core mission hasn’t changed at all, except to spring into action to make our own contribution to fighting the coronavirus.
This latest CIRM Annual Reportcovers 2019 through June 30, 2020. Why? Well, as you probably know we are running out of money and could be funding our last new awards by the end of this year. So, we wanted to produce as complete a picture of our achievements as we could – keeping in mind that we might not be around to produce a report next year.
It’s a pretty jam-packed report. It covers everything from the 14 new clinical trials we have funded this year, including three specifically focused on COVID-19. It looks at the extraordinary researchers that we fund and the progress they have made, and the billions of additional dollars our funding has helped leverage for California. But at the heart of it, and at the heart of everything we do, are the patients. They’re the reason we are here. They are the reason we do what we do.
There are stories of people like Byron Jenkins who almost died from multiple myeloma but is now back leading a full, active life with his family thanks to a CIRM-funded therapy with Poseida. There is Jordan Janz, a young man who once depended on taking 56 pills a day to keep his rare disease, cystinosis, under control but is now hoping a stem cell therapy developed by Dr. Stephanie Cherqui and her team at UC San Diego will make that something of the past.
These individuals are remarkable on so many levels, not the least because they were willing to be among the first people ever to try these therapies. They are pioneers in every sense of the word.
There is a lot of information in the report, charting the work we have done over the last 18 months. But it’s also a celebration of everyone who made it possible, and our way of saying thank you to the people of California who gave us this incredible honor and opportunity to do this work.
You can’t look at this photo and not smile. This is Evie Vaccaro, and it’s clear she is just bursting with energy and vitality. Sometimes it feels like I have known Evie all her life. In a way I have. And I feel so fortunate to have done so, and that’s why this photo is so powerful, because it’s a life that almost ended before it had a chance to start.
Evie was born with a rare condition called Severe Combined Immunodeficiency (SCID). Children with this condition lack a functioning immune system so even a simple cold or diaper rash can prove fatal. Imagine how perilous their lives are in a time of COVID-19. These children used to be called “bubble babies” because they were often kept inside sterile plastic bubbles to keep them alive. Many died before their second birthday.
Today there is no need for plastic bubbles. Today, we have a cure. That’s a word we use very cautiously, but in Evie’s case, and the case of more than 40 other children, we use it with pride.
Dr. Don Kohn at UCLA has developed a method of taking the child’s own blood stem cells and, in the lab, inserting a corrected copy of the gene that caused SCID, and then returning those cells to the child. Because they are stem cells they multiply and renew and replicate themselves, creating a new blood supply, one free of the SCID mutation. The immune system is restored. The children are cured.
This is a story we have told several times before, but we mention it again because, well, it never gets old, and because Evie is on the front and back cover of our upcoming Annual Report. The report is actually a look back on the last 18 months in CIRM’s life, reporting on the progress we have made in advancing stem cell research, in saving and changing lives, and in producing economic benefits for California (billions of dollars in sales revenue and taxes and thousands of jobs).
Evie’s story, Evie’s photo, is a reminder of what is possible thanks to the voters of California who created CIRM back in 2004. Hers is just one of the stories in the report. I think, you’ll enjoy reading all of them.
This past Thursday the governing Board of the California Institute for Regenerative Medicine (CIRM) were presented with an update on CIRM’s clinical portfolio, which to date includes 60 clinical trials in various areas including kidney failure, cancer, and other rare diseases. The full President’s Report gives an update on 15 of these trials, in addition to our landmark Cure Sickle Cell Initiative with the NIH and our various educational programs.
Although we won’t be diving into extensive detail for all of these trials, we wanted to highlight several key updates made in this presentation to demonstrate how our clinical portfolio is maturing, with many of these trials moving towards registration. Classically, registration trials are large Phase 3 trials. Notably, some of the highlighted CIRM trials are small Phase 2 or earlier trials that seek to gain enough safety and efficacy data to support final FDA marketing approval. This is a trend with regenerative medicine programs where trial sizes are often small due to the fact that the affected populations are so small with some of these rare diseases. Despite this, the approaches could allow a so called “large effect size,” meaning the signal of clinical benefit per patient is strong enough to give a read of whether the therapy is working or not. CIRM programs often address rare unmet needs and utilize this approach.
For example, Orchard Therapeutics, which is conducting a phase 2 clinical trial for ADA Severe Combined Immunodeficiency (ADA-SCID), a rare immune disorder caused by a genetic mutation, has shown a long-term recovery of the immune system in 20 patients two years post treatment. Orchard plans to submit a Biologics License Application (BLA) sometime in 2020, which is the key step necessary to obtain final approval from the Food and Drug Administration (FDA) for a therapy.
“We are thrilled to see encouraging results for this genetically modified cell therapy approach and a path forward for FDA approval,” says Maria T. Millan, MD, President and CEO of CIRM. “CIRM is proud of the role it has played in this program. We funded the program while it was at UCLA and it is now in partnership with Orchard Therapeutics as it takes the program through this final phase toward FDA marketing approval. Success in this program is a game changer for patients with ADA-SCID who had no other options and who had no bone marrow transplant donors. It also opens up possibilities for future approaches for this dieaseas as well as the other 6,000 genetic diseases that currently have no treatment.”
The trial uses a gene therapy approach that takes the patient’s own blood stem cells, introduces a functional version of the ADA gene, and reintroduces these corrected blood stem cells back into the patient. From blood tests, one can readily detect whether the approach is successful from the presence of ADA and from the presence of immune cells that were not previously present. To date, it has been awarded approximately $19 million in CIRM funding. Additionally, it has received FDA Breakthrough Therapy as well as Orphan Drug Designations, both of which are designed to accelerate the development of the treatment.
Another trial that was highlighted is Rocket Pharmaceutical’s clinical trial for Leukocyte Adhesion Deficiency-1 (LAD-1), a rare and fatal pediatric disease that affects the body’s ability to combat infections. They have just released initial results from their first patient. This is also a gene therapy approach using the patient’s own blood stem cells. The notable aspect of this trial is that the investigators designed this small phase 1 trial of nine patients to be “registration enabling.” This means that, if they find compelling data, they intend to bring the experience and data from this trial to the FDA to seek agreement on what would be required to get final marketing approval in order to get this treatment to patients with severe unmet medical needs in the most timely way possible.
Preliminary results demonstrate early evidence of safety and potential efficacy. There were visible improvements in multiple disease-related skin lesions after receiving the therapy. They are collecting more data on more patients. To date, it has received $6.6 million in CIRM funding.
As a unique immuno-oncology approach (using the body’s immune system to battle cancer), CIRM is funding Forty Seven Inc. to conduct a clinical trial for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), both of which are forms of cancer. They have received Fast Track and Orphan Drug designation from the FDA.
The trial is using an antibody blocking CD47, a “don’t eat me” signal, which allows the body’s own immune cells to seek and destroy cancerous stem cells. This is combined with chemotherapy to render the cancer stem cells more susceptible to immune destruction. This trial has received $5 million in CIRM funding thus far.
Other registration phase trials in the CIRM portfolio include the following Phase 3 trials:
Brainstorm Cell Therapeutics, for a fatal debilitating neurodegenerative disease, Amyotrophic Lateral Sclerosis (Lou Gehrig’s disease). That company has completed enrollment and expects top line results in the final quarter of 2020.
Humacyte, which is testing bioengineered de-cellularized vessels that are implanted to create vascular access that is repopulated by the patients own stem cells to make it more like native vessel. The company is conducting two Phase 3 trials to compare this bioengineered vessel to synthetic grafts and to the patients’ own vessels for use in hemodialysis, a “life line” for patients with end stage renal disease. Humacyte was the first US FDA Cell Therapy program to receive the Regenerative Medicine Advanced Technologies (RMAT) in March 2017. To date, these trials have been awarded $24 million in CIRM funding.
Medeor Therapeutics has received $11.2M in CIRM funding to conduct a Phase 3 trial in combined blood stem cell and kidney transplantation to induce immunologic tolerance so that the blood stem cells teach the patient’s immune system to recognize the transplanted kidney as its own. The goal is to remove the need for chronic immunosuppressive medications, that have its own complications. If successful, transplant recipients would not need to “trade one chronic condition for another.”
A few years ago, Brenden Whittaker was running out of time. Brenden was born with a rare condition called x-linked chronic granulomatous disease or XCGD. It meant he lacked a critical part of his immune system that protects against bacterial or fungal infections.
Over 22 years Brenden was in and out of the hospital hundreds of times. Twice he almost died. When antibiotics failed to clear up persistent infections surgeons had to remove parts of his lungs and liver.
Brenden felt he was running out of options. Then he signed up for a clinical trial (funded by CIRM) that would use his own stem cells to correct the problem. More than four years later Brenden is doing just fine.
And he’s not the only one. A new study, published in the journal Nature Medicine, shows that six other patients in the clinical trial are now in remission and have stopped taking any other medications.
Don Kohn, the lead researcher on the team from UCLA’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, says that in the past the only “cure” for people with CGD was a bone marrow transplant, but that was rarely an option for most patients. In a news release he said finding a perfect match for a transplant was difficult, and even then, patients had to take powerful anti-rejection medications to stop their body rejecting the transplant. So, they developed another approach, using genetically re-engineered stem cells from the patient themselves.
“With this gene therapy, you can use a patient’s own stem cells instead of donor cells for a transplant. This means the cells are perfectly matched to the patient and it should be a much safer transplant, without the risks of rejection.”
The team removed blood stem cells from the patients and, in the lab, corrected the genetic mutation that caused CGD. They then returned those cells to the patients which, because they are stem cells, multiplied and created a new blood supply – one free of CGD – and repaired the immune system.
Brenden was the first of five patients treated in the US. Another four were treated in Europe. All were between the ages of 2 and 27 (CGD patients often die in their 20’s because of the impact of repeated infections).
Two patients died because of previously incurred infections
Six of the seven surviving patients have discontinued previous treatments
Four new patients have since been treated and are currently free of infections
Dr. Kohn said the results are really encouraging: “None of the patients had complications that you might normally see from donor cells and the results were as good as you’d get from a donor transplant — or better.”
The next step is for the researchers to work with the US Food and Drug Administration to get permission to carry out a larger trial, with the eventual goal of getting approval to make it available to all patients who need it.
Regular readers of our blog will remember that Don Kohn also pioneered a similar approach in treating, and curing, children battling another rare immune disorder, severe combined immunodeficiency or SCID. You can read about that here.
As for Brenden, he is now in college and has his sights set on medical school. In 2016 we profiled him in our Annual Report and ran a long interview with him on the blog where he talked about the joys of mowing the lawn and learning to live without a deadly disease stalking him.
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: 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.
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: 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.
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.
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.
Is there any stem cell therapy for optical nerve damage? Deanna Rice
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
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.
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.
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.
What advances have been made using stem cells for the treatment of Type 2 Diabetes?Mary Rizzo
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.
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.
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.
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.
What is happening with Parkinson’s research? Hanifa Gaphoor
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.
Any plans for Huntington’s?Nikhat Kuchiki
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)
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.
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: 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.
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: 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.
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?
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.
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.
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.
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.
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.
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.
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.
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.
satisfying to see two projects you have supported for a long time do well. That’s
particularly true when the projects in question are targeting conditions that
have no other effective therapies.
This week we learned
that a clinical trial we funded to help people with spinal cord injuries
continues to show benefits. This trial holds a special place in our hearts
because it is an extension of the first clinical trial we ever funded.
Initially it was with Geron,
and was later taken up by Asterias
Biotherapeutics, which has seen been bought by Lineage Cell Therapeutics Inc.
The therapy involved transplanting oligodendrocyte progenitor cells (OPCs), which are derived from human embryonic stem cells, into people who suffered recent spinal cord injuries that left them paralyzed from the neck down. OPCs play an important role in supporting and protecting nerve cells in the central nervous system, the area damaged in a spinal cord injury. It’s hoped the cells will help restore some of the connections at the injury site, allowing patients to regain some movement and feeling.
In a news
release, Lineage said that its OPC
therapy continues to report positive results, “where the overall safety profile
of OPC1 has remained excellent with robust motor recovery in upper extremities
maintained through Year 2 patient follow-ups available to date.”
Two years in the
patients are all continuing to do well, and no serious unexpected side effects
have been seen. They also reported:
– Motor level improvements
Five of six Cohort 2 patients achieved
at least two motor levels of improvement over baseline on at least one side as
of their 24-month follow-up visit.
In addition, one Cohort 2 patient
achieved three motor levels of improvement on one side over baseline as of the
patient’s 24-month follow-up visit; improvement has been maintained through the
patient’s 36-month follow-up visit.
Brian M. Culley, CEO of Lineage Cell Therapeutics called the news “exciting”, saying “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.”
The other good news came from Orchard Therapeutics, a company we have
partnered with on a therapy for Severe Combined Immunodeficiency (SCID) also
known as “bubble baby diseases” (we have blogged about this a lot including
In a news
release Orchard announced that the European Medicines Agency (EMA) has granted an accelerated
assessment for their gene therapy for metachromatic leukodystrophy (MLD). This
is a rare and often fatal condition that results in the build-up of sulfatides
in the brain, liver, kidneys and other organs. Over time this makes it harder
and harder for the person to walk, talk, swallow or eat.
Anne Dupraz-Poiseau, chief regulatory
officer of Orchard Therapeutics, says this is testimony to the encouraging
early results of this therapy. “We look forward to working with the EMA to
ensure this potentially transformative new treatment, if approved, reaches
patients in the EU as quickly as possible, and continuing our efforts to expand
patient access outside the EU.”
The accelerated assessment potentially
provides a reduced review timeline from 210 to 150 days, meaning it could be
available to a wider group of patients sooner.
An independent Economic Impact Report says the California Institute for Regenerative Medicine (CIRM) has had a major impact on California’s economy, creating tens of thousands of new jobs, generating hundreds of millions of dollars in new taxes, and producing billions of dollars in additional revenue for the state.
The report, done by Dan Wei and Adam Rose at the Price School of Public Policy at the University of Southern California, looked at the impacts of CIRM funding on both the state and national economy from the start of the Stem Cell Agency in 2004 to the end of 2018.
The total impacts on the California economy are estimated
billion of additional gross output (sales revenue)
million of additional state/local tax revenues
million of additional federal tax revenues
additional full-time equivalent (FTE) jobs, half of which offer salaries
considerably higher than the state average
Millan, M.D., CIRM’s President and CEO, says the report reflects the Agency’s
role in building an ecosystem to accelerate the translation of important stem
cell science to solutions for patients with unmet medical needs. “CIRM’s
mission on behalf of patients has been the priority from day one, but this
report shows that CIRM funding brings additional benefits to the state. This report
reflects how CIRM is promoting economic growth in California by attracting
scientific talent and additional capital, and by creating an environment that
supports the development of businesses and commercial enterprises in the state”
In addition to the benefits to California, the impacts
outside of California on the US economy are estimated to be:
billion of additional gross output (sales revenue)
million of additional state (non-Californian) & local tax revenue
million of additional federal tax revenues
additional full-time equivalent (FTE) jobs
researchers summarize their findings, saying: “In terms of economic impacts, the
state’s investment in CIRM has paid handsome dividends in terms of output, employment,
and tax revenues for California.”
The estimates in the report are based on the economic stimulus
created by CIRM funding and by the co-funding that researchers and companies
were required to provide for clinical and late-stage preclinical projects. The
estimates also include:
Investments in CIRM-supported projects from private funders such
as equity investments, public offerings and mergers and acquisitions,
Follow-on funding from the National Institutes of Health and other
organizations due to data generated in CIRM-funded projects
Funding generated by clinical trials held at CIRM’s Alpha Stem
Cell Clinics network
researchers state “Nearly half of these impacts emanate from the $2.67 billion
CIRM grants themselves.”
economic impact of California’s investment in stem and regenerative cell
research is reflective of significant progress in this field that was just
being born at the time of CIRM’s creation,” says Dr. Millan. “We fund the most
promising projects based on rigorous science from basic research into clinical
trials. We partnered with researchers and companies to increase the likelihood
of success and created specialized infrastructure such as the Alpha Clinics
Network to support the highest quality of clinical care and research standards
for these novel approaches. The
ecosystem created by CIRM has attracted scientists, companies and capital from outside
the state to California. By supporting promising science projects early on,
long before most investors were ready to come aboard, we enabled our scientists
to make progress that positioned them to attract significant commercial
investments into their programs and into California.”
think one of the greatest strengths of CIRM has been their focus on development
of new stem cell therapies that can become real medicines,” says UCLA and
Orchard Therapeutics’ Don Kohn, M.D. “This has meant guiding academic
investigators to do the things that may be second nature in
industry/pharmaceutical companies but are not standard for basic or clinical
research. The support from CIRM to perform the studies and regulatory
activities needed to navigate therapies through the FDA and to form alliances
with biotech and pharma companies has allowed the stem cell gene therapy we
developed to treat SCID babies to be advanced and licensed to Orchard
Therapeutics who can make it available to patients across the country.”
support has been instrumental to our early successes and our ability to rapidly
progress Forty Seven’s CD47 antibody targeting approach with magrolimab,” says
Mark Chao, M.D., Ph.D., Founder and Vice President of Clinical Development at
Forty Seven Inc. “ CIRM was an early collaborator in our clinical
programs, and will continue to be a valued partner as we move forward with our
MDS/AML clinical trials.”
researchers say the money generated by partnerships and investments, what is
called “deal-flow funding”, is still growing and that the economic benefits
created by them are likely to continue for some time: “Deal-flow funding
usually involves several waves or rounds of capital infusion over many years,
and thus is it expected that CIRM’s past and current funding will attract
increasing amounts of industry investment and lead to additional spending
injections into the California economy in the years to come.”
They conclude their report by saying: “CIRM has led to
California stem cell research and development activities becoming a leader
among the states.”