How the Tooth Fairy is helping unlock the secrets of autism

Our 2021-22 Annual Report is now online. It’s filled with information about the work we have done over the last year (we are on a fiscal calendar year from July 1 – June 30), the people who have helped us do that work, and some of the people who have benefited from that work. One of those is Dr. Alysson Muotri, a professor in the Departments of Pediatrics and Cellular & Molecular Medicine at the University of California, San Diego.

Dr. Alysson Muotri, in his lab at UCSD

For Dr. Alysson Muotri, trying to unlock the secrets of the brain isn’t just a matter of scientific curiosity, it’s personal. He has a son with autism and Dr. Muotri is looking for ways to help him, and millions of others like him around the world.

He created the Tooth Fairy project where parents donated more than 3,000 baby teeth from  children with autism and children who are developing normally. Dr. Muotri then turned cells from those teeth into neurons, the kind of brain cell affected by autism. He is using those cells to try and identify how the brain of a child with autism differs from a child who is developing normally.

“We’ve been using cells from this population to see what are the alterations (in the gene) and if we can revert them back to a normal state. If you know the gene that is affected, and autism has a strong genetic component, by genome sequencing you can actually find what are the genes that are affected and in some cases there are good candidates for gene therapy. So, you just put the gene back. And we can see that in the lab where we are correcting the gene that is mutated, the networks start to function in a way that is more neurotypical or normal. We see that as highly promising, there’s a huge potential here to help those individuals.”

He is also creating brain organoids, three-dimensional structures created from stem cells that mimic some of the actions and activities of the brain. Because these are made from human cells, not mice or other animals, they may be better at indicating if new therapies have any potential risks for people.

“We can test drugs in the brain organoids of the person and see if it works, see if there’s any toxicity before you actually give the drug to a person, and it will save us time and money and will increase our knowledge about the human brain.”

He says he still gets excited seeing how these cells work. “It’s amazing, it’s a miracle. Every time I see it, it’s like seeing dolphins in the sea because it’s so beautiful.”

Dr. Muotri is also a big proponent of diversity, equity and inclusion in scientific research. He says in the past it was very much a top-down model with scientists deciding what was important. He says we need to change that and give patients and communities a bigger role in shaping the direction of research.

“I think this is something we scientists have to learn, how to incorporate patients in our research. These communities are the ones we are studying, and we need to know what they want and not assume that what we want is what they want. They should be consulted on our grants, and they should participate in the design of our experiments. That is the future.”

So far, some encouraging news for stem cell clinical trial treating epilepsy

Neurona Therapeutics is testing a new therapy for a drug-resistant form of epilepsy and has just released some encouraging early findings. The first patient treated went from having more than 30 seizures a month to just four seizures over a three-month period.

This clinical trial, funded by the California Institute for Regenerative Medicine (CIRM), is targeting  mesial temporal lobe epilepsy (MTLE), one of the most common forms of epilepsy. Because the seizures caused by MTLE are frequent, they can be particularly debilitating and increase the risk of a decreased quality of life, depression, anxiety and memory impairment.

Neurona’s therapy, called NRTX-1001, consists of a specialized type of neuronal cell derived from embryonic stem cells.  Neuronal cells are messenger cells that transmit information between different areas of the brain, and between the brain and the rest of the nervous system.

NRTX-1001 is injected into the brain in the area affected by the seizures where it releases neurotransmitters or chemical messengers that will block the signals in the brain causing the epileptic seizures.

The first patient treated had a nine-year history of epilepsy and, despite being on anti-epileptic medications, was experiencing dozens of seizures a month. Since the therapy he has had only four seizures in three months. The therapy hasn’t produced any serious side effects.

In a news release Dr. Cory Nicholas, Neurona’s President and CEO, said while this is only one patient, it’s good news.

“The reduced number of seizures reported by the first person to receive NRTX-1001 is very encouraging, and we remain cautiously optimistic that this reduction in seizure frequency will continue and extend to others entering this cell therapy trial. NRTX-1001 administration has been well tolerated thus far in the clinic, which is in line with the extensive preclinical safety data collected by the Neurona team. With recent clearance from the Data Safety Monitoring Board we are excited to continue patient enrollment. We are very grateful to these first participants, and thank the clinical teams for the careful execution of this pioneering study.”

CIRM has been a big supporter of this work from the early Discovery stage work to this clinical trial. That’s because when we find something promising, we want to do everything we can to help it live up to its promise.

From our house to the White House. Kinda

Jackie Ward, PhD. Photo courtesy National Institute of Neurological Diseases and Stroke

It’s always fun to meet someone early in their career and see how they grow and evolve and take on new challenges.

I first met Jackie Ward when she received a training grant from CIRM while she studied for her PhD at the University of California, San Diego. Jackie offered to write blogs for us about her experience and they were always fun, informative, elegantly written and very engaging. Fast forward a few years and Jackie became a part of Americans For Cures, then she became Chief of Staff at the National Institute of Neurological Disorders and Stroke (NINDS), and finally – at least so far – she took on the role of Assistant Director at the White House Office of Science and Technology Policy (OSTP).

Not too shabby eh.

So, I reached out to Jackie and asked her some questions about her work and career. She generously put aside keeping the nation healthy to answer them. Enjoy.

  1. What made you decide to move from research into government.

I think if you asked my high school government teacher (shout out to Mr. Bell!), he would be the least surprised person that I have ended up where I am currently. I was always interested in topics and activities beyond science, but at a certain point you have to choose a path. When it came time to deciding my undergraduate major, I figured that if I pursued my interest in biology it would still keep my options open to do something different in my career, but if I chose to be a French major, or Political Science major, or English major – I might close the door in my ability to pursue scientific research. When I got to graduate school, I saw the impact of government (both state and federal) decisions on work in the lab. This takes the form of where funding goes, but also in the rules you have to follow while doing research. Though I liked the pursuit of new knowledge and being the one designing and performing experiments, I was interested in understanding more about how those government decisions are made upstream of the lab bench.

  1. What’s the most surprising thing you have learned in your time at the White House Office of Science and Technology Policy (OSTP).

Maybe not “surprising” but the thing that may not be obvious to outsiders: OSTP’s budget is tiny compared to other Executive Branch agencies (like where I came from previously at NIH). The work we accomplish in this office is solely by forming partnerships and collaborations with others across the government. We are not typically the rowers of the boat, but we can be the steerer or navigator. (Is the term coxswain? I have never been on a crew team obviously.)

  1. Was it hard making the transition from research to advocacy and now policy?

Honestly I feel like my training in research set me up well for the jobs I’ve had in policy. There is often not someone telling you exactly how to do something – you have to do the work yourself to search the literature, talk to other people, find collaborators, and keep at it. And the skills that you hone in research – from keeping an organized lab notebook the whole way through to writing scientific papers – are some of the same skills you need in government. 

  1. At a time when so many people seem so skeptical of science how do you get your message out.

We have to meet people where they are. As a government official, I have great respect for messages that come from experts within the government – but that is not the only way the message should be getting out. Scientists and other experts within communities should also be spokespeople for science. I would urge scientists at every level – whether you are a citizen scientist, a medical doctor, a PhD student, or some other kind of expert – to engage with their communities and put the work in to understand how to effectively communicate at levels beyond just speaking to your colleagues.

  1. One of the issues that so many of us, including here at CIRM, are working on is improving our performance in diversity, equity and inclusion. How big an issue is that for you and your colleagues at OSTP and what are you doing to try and address it.

The mission of our office is to “maximize the benefits of science and technology to advance health, prosperity, security, environmental quality, and justice for all Americans.” Those final two words are key: “all Americans.” It is the policy of this Office and our Administration that it is not okay for the benefits of science & technology to only reach a select few – who can afford it or who live in a certain zip code or who know the right people. 

This takes different forms depending on what kind of S&T work we are talking about, but I will give you an example from my own work. I have been leading an effort that aims to explore and act upon how digital health care delivery technologies can be used to increase access to healthcare in community-based health settings. We know that these cutting edge technologies are most likely to get to people who, for example, get their care at academic medical centers, or who have primo health insurance plans, or who are already tech savvy. We feel that as these technologies continue to grow within the healthcare system, that it is an imperative to ensure that they are accessible to practitioners and patients at community health centers, or to people who may not be tech geeks, or that they can be interoperable with the systems used by community health workers.

  1. During a time of Covid and now Monkeypox, what’s it like to have a front row seat and watch how government responds to public health emergencies.

My colleagues who work on outbreaks and pandemic responses are some of the most dedicated public servants I know. They will be the first to admit that we are continually learning and integrating new tools and technologies into our toolbox, and that is a constant effort. Emergent issues like outbreaks force decisions when there may not be a lot of information – that is a hard job.  

  1. I’ve always felt that DC would be a fun place to live and work (except during the height of summer!) what do you most like about it.

DC is a city full of people who care deeply (almost to a pathological extent) about the work they do and how to make the world a better place. There’s also incredible diversity here – which means a variety of viewpoints, languages, and food! I love that.

Jackie is not just a good writer. She’s also a great speaker. Here’s a clip of her responding to our Elevator Challenge many years ago, when she was still a fledgling researcher. Her explanation of what she does, is a master class in turning a complex subject into something easy to understand.

Fighting for his life and the lives of other stroke survivors

Sean Entin, stroke survivor and founder of Stroke Hacker

The word “miraculous” gets tossed around a lot in the world of medicine, mostly by people who have made an unexpected recovery from a deadly or life-threatening condition. In Sean Entin’s case calling his recovery from an almost-fatal stroke could be called miraculous, but I think you would also have to say it’s due to hard work, determination, and an attitude that never even considered giving up.

Sean had a stroke in 2011. Doctors didn’t think he’d survive. He was put into a coma and underwent surgery to create an opening in his skull to give his brain time and space to heal. When he woke he couldn’t walk or talk, couldn’t count. Doctors told him he would never walk again.

They didn’t know Sean. Fast forward to today. Sean is active, has completed two 5k races – that’s two more than me – and has created Stroke Hacker, a program designed to help others going through what he did.

Sean is a remarkable man, which is why I sat down to chat with him for the latest episode of the California Institutes for Regenerative Medicine’s podcast, ‘Talking ‘Bout (re)Generation’.

He is a fascinating man, and he makes for fascinating company. Enjoy the podcast.

The California Institute for Regenerative Medicine (CIRM) has invested more than $80 million in stroke research, including one clinical trial currently underway.

The present and future of regenerative medicine

One of the great pleasures of my job is getting to meet the high school students who take part in our SPARK or Summer Internship to Accelerate Regenerative Medicine Knowledge program. It’s a summer internship for high school students where they get to spend a couple of months working in a world class stem cell and gene therapy research facility. The students, many of whom go into the program knowing very little about stem cells, blossom and produce work that is quite extraordinary.

One such student is Tan Ieng Huang, who came to the US from China for high school. During her internship at U.C. San Francisco she got to work in the lab of Dr. Arnold Kriegstein. He is the Founding Director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at the University of California, San Francisco. Not only did she work in his lab, she took the time to do an interview with him about his work and his thoughts on the field.

It’s a fascinating interview and shows the creativity of our SPARK students. You will be seeing many other examples of that creativity in the coming weeks. But for now, enjoy the interview with someone who is a huge presence in the field today, by someone who may well be a huge presence in the not too distant future.

‘a tête-à-tête with Prof. Arnold Kriegstein’

The Kriegstein lab team: Photo courtesy UCSF

Prof. Arnold Kriegstein is the Founding Director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at the University of California, San Francisco. Prof. Kriegstein is also the Co-Founder and Scientific Advisor of Neurona Therapeutics which seeks to provide effective and safe cell therapies for chronic brain disorder. A Clinician by training, Prof. Kriegstein has been fascinated by the intricate workings of the human brain. His laboratory focuses on understanding the transcriptional and signaling networks active during brain development, the diversity of neuronal cell types, and their fate potential. For a long time, he has been interested in harnessing this potential for translational and therapeutic intervention.

During my SEP internship I had the opportunity to work in the Kriegstein lab. I was in complete awe. I am fascinated by the brain. During the course of two months, I interacted with Prof. Kriegstein regularly, in lab meetings and found his ideas deeply insightful. Here’s presenting some excerpts from some of our discussions, so that it reaches many more people seeking inspiration!

Tan Ieng Huang (TH): Can you share a little bit about your career journey as a scientist?

Prof. Arnold Kriegstein (AK): I wanted to be a doctor when I was very young, but in high school I started having some hands-on research experience. I just loved working in the lab. From then on, I was thinking of combining those interests and an MD/PhD turned out to be an ideal course for me. That was how I started, and then I became interested in the nervous system. Also, when I was in high school, I spent some time one summer at Rockefeller University working on a project that involved operant conditioning in rodents and I was fascinated by behavior and the role of the brain in learning and memory. That happened early on, and turned into an interest in cortical development and with time, that became my career.

TH: What was your inspiration growing up, what made you take up medicine as a career?

AK: That is a little hard to say, I have an identical twin brother. He and I used to always share activities, do things together. And early on we actually became eagle scouts, sort of a boy scout activity in a way. In order to become an eagle scout without having to go through prior steps, we applied to a special program that the scouts had, which allowed us to shadow physicians in a local hospital. I remember doing that at a very young age. It was a bit ironic, because one of the evenings, they showed us films of eye surgery, and my brother actually fainted when they made an incision in the eye. The reason it makes me laugh now is because my brother became an eye surgeon many years later. But I remember our early experience, we both became very fascinated by medicine and medical research.

Tan Ieng and Dr. Arnold Kriegstein at UCSF

TH: What inspired you to start the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research Institute?

AK: My interest in brain development over the years became focused on earlier stages of development and eventually Neurogenesis, you know, how neurons are actually generated during early stages of in utero brain development. In the course of doing that we discovered that the radial glial cells, which have been thought for decades to simply guide neurons as they migrate, turned out to actually be the neural stem cells, they were making the neurons and also guiding them toward the cortex. So, they were really these master cells that had huge importance and are now referred to as neural stem cells. But at that time, it was really before the stem cell field took off. But because we studied neurogenesis, because I made some contributions to understanding how the brain develops from those precursors or progenitor cells, when the field of stem cells developed, it was very simple for me to identify as someone who studied neural stem cells. I became a neural stem cell scientist. I started a neural stem cell program at Columbia University when I was a Professor there and raised 15 million dollars to seed the program and hired new scientists. It was shortly after that I was approached to join UCSF as the founder of a new stem cell program. And it was much broader than the nervous system; it was a program that covered all the different tissues and organ systems.

TH: Can you tell us a little bit about how stem cell research is contributing to the treatment of diseases? How far along are we in terms of treatments?

AK: It’s taken decades, but things are really starting to reach the clinic now. The original work was basic discovery done in research laboratories, now things are moving towards the clinic. It’s a really very exciting time. Initially the promise of stem cell science was called Regenerative medicine, the idea of replacing injured or worn-out tissues or structures with new cells and new tissues, new organs, the form of regeneration was made possible by understanding that there are stem cells that can be tweaked to actually help make new cells and tissues. Very exciting process, but in fact the main progress so far hasn’t been replacing worn out tissues and injured cells, but rather understanding diseases using human based model of disease. That’s largely because of the advent of induced pluripotent stem cells, a way of using stem cells to make neurons or heart cells or liver cells in the laboratory, and study them both in normal conditions during development and in disease states. Those platforms which are relatively easy to make now and are pretty common all over the world allow us to study human cells rather than animal cells, and the hope is that by doing that we will be able to produce conventional drugs and treatments that work much better than ones we had in the past, because they will be tested in actual human cells rather than animal cells.

TH: That is a great progress and we have started using human models because even though there are similarities with animal models, there are still many species-specific differences, right?

AK: Absolutely, in fact, one of the big problems now in Big Pharma, you know the drug companies, is that they invest millions and sometimes hundreds of millions of dollars in research programs that are based on successes in treating mice, but patients don’t respond the same way. So the hope is that by starting with a treatment that works on human cells it might be more likely that the treatment will work on human patients.

TH: What are your thoughts on the current challenges and future of stem cell research?

AK: I think this is an absolute revolution in modern medicine, the advent of two things that are happening right now, first the use of induced pluripotent stem cells, the ability to make pluripotent cells from adult tissue or cells from an individual allows us to use models of diseases that I mentioned earlier from actual patients. That’s one major advance. And the other is gene editing, and the combination of gene editing and cell-based discovery science allows us to think of engineering cells in ways that can make them much more effective as a form of cell therapy and those cell therapies have enormous promise. Right now, they are being used to treat cancer, but in the future, they might be able to treat heart attack, dementia, neurodegenerative diseases, ALS, Parkinson’s disease, a huge list of disorders that are untreatable right now or incurable. They might be approached by the combination of cell-based models, cell therapies, and gene editing.

TH: I know there are still some challenges right now, like gene editing has some ethical issues because people don’t know if there can be side effects after the gene editing, what are your thoughts?

AK: You know, like many other technologies there are uncertainties, and there are some issues. Some of the problems are off-target effects, that is you try to make a change in one particular gene, and while doing that you might change other genes in unexpected ways and cause complications. But we are understanding that more and more now and can make much more precise gene editing changes in just individual genes without affecting unanticipated areas of the genome. And then there are also the problems of how to gene-edit cells in a safe way. There are certain viral factors that can be used to introduce the gene editing apparatus into a cell, and sometimes if you are doing that in a patient, you can also have unwanted side effects from the vectors that you are using, often they are modified viral vectors. So, things get complicated very quickly when you start trying to treat patients, but I think these are all tractable problems and I think in time they will all be solved. It will be a terrific, very promising future when it comes to treating patients who are currently untreatable.

TH: Do you have any advice for students who want to get into this field?

AK: Yes, I think it’s actually never been a better time and I am amazed by the technologies that are available now. Gene editing that I mentioned before but also single cell approaches, the use of single cell multiomics revealing gene expression in individual cells, the molecular understanding of how individual cells are formed, how they are shaped, how they change from one stage to another, how they can be forced into different fates. It allows you to envision true Regenerative medicine, improving health by healing or replacing injured or diseased tissues. I think this is becoming possible now, so it’s a very exciting time. Anyone who has an interest in stem cell biology or new ways of treating diseases, should think about getting into a laboratory or a clinical setting. I think this time is more exciting than it’s ever been.

TH: So excited to hear that, because in school we have limited access to the current knowledge, the state-of-art. I want to know what motivates you every day to do Research and contribute to this field?

AK: Well, you know that I have been an MD/PhD, as I mentioned before, in a way, there are two different reward systems at play. In terms of the PhD and the science, it’s the discovery part that is so exciting. Going in every day and thinking that you might learn something that no one has ever known before and have a new insight into a mechanism of how something happens, why it happens. Those kinds of new insights are terrifically satisfying, very exciting. On the MD side, the ability to help patients and improve peoples’ lives is a terrific motivator. I always wanted to do that, was very driven to become a Neurologist and treat both adult and pediatric patients with neurological problems. In the last decade or so, I’ve not been treating patients so much, and have focused on the lab, but we have been moving some of our discoveries from the laboratory into the clinic. We have just started a clinical trial, of a new cell-based therapy for epilepsy in Neurona Therapeutics, which is really exciting. I am hoping it will help the patients but it’s also a chance to actually see something that started out as a project in the laboratory become translated into a therapy for patients, so that’s an achievement that has really combined my two interests, basic science, and clinical medicine. It’s a little late in life but not too late, so I’m very excited about that.

Tan Ieng Huang, Kriegstein Lab, SEP Intern, CIRM Spark Program 2022

First patient dosed in clinical trial for a drug-resistant form of epilepsy

Tablet BM47753. Neo-Babylonian Period. Courtesy of the British Museum, London.

Epilepsy seems to have been a problem for people for as long as people have been around. The first recorded mention of it is on a 4000-year-old Akkadian tablet found in Mesopotamia (modern day Iraq). The tablet includes a description of a person with “his neck turning left, hands and feet are tense, and his eyes wide open, and from his mouth froth is flowing without him having any consciousness.”

Despite that long history, effective treatments for epilepsy were a long time coming. It wasn’t till the middle of the 19th century that physicians started using bromides to help people with the condition, but they also came with some nasty side effects, including depression, weakness, fatigue, lethargy, and coma.

Fast forward 150 years or so and we are now, hopefully, entering a new era. This week, Neurona Therapeutics announced they had dosed the first patient in their first-in-human clinical trial formesial temporal lobe epilepsy (MTLE), the most common form of focal epilepsy in adults. The trial specifically targets people who have a drug-resistant form of MTLE.

Neurona has developed a therapy called NRTX-1001, consisting of a specialized type of neuronal or brain cell derived from embryonic stem cells.  These cells are injected into the brain in the area affected by the seizures where they release a neurotransmitter or chemical messenger that will block the signals in the brain causing the epileptic seizures. Pre-clinical testing suggests a single dose of NRTX-1001 may have a long-lasting ability to suppress seizures.

A new approach is very much needed because current therapies for drug-resistant epilepsy are only partially effective and have serious drawbacks. One treatment that can significantly reduce seizure frequency is the removal of the affected part of the brain, however this can cause serious, irreversible damage, such as impacting memory, mood and vision.

CIRM has a vested interest in seeing this therapy succeed. We have invested more than $14 million over four different awards, in helping this research progress from a basic or Discovery level through to the current clinical trial.

In a news release, two key figures in administering the first dose to a patient said this was an important step forward. 

Harish Babu, M.D., Ph.D., assistant professor of neurosurgery at SUNY Upstate Medical University said: “Neurona’s regenerative cell therapy approach has the potential to provide a single-administration, non-destructive alternative for the treatment of drug-resistant focal epilepsy. Currently, people with mesial temporal lobe epilepsy who are not responsive to anti-seizure medications have few options, such as an invasive surgery that removes or destroys the affected brain tissue.”

Robert Beach, M.D., Ph.D. professor of neurology at SUNY Upstate Medical University added: “The objective of NRTX-1001 is to add cells that have the potential to repair the circuits that are damaged in epilepsy and thus reduce seizure activity.”

There is a huge unmet medical need for an effective, long-term therapy. Right now, it’s estimated that three million Americans have epilepsy, and 25 to 35 percent live with ongoing seizures despite dozens of approved drugs on the market.

If this therapy works it might mean that 4,000 year old tablet will become a medical footnote, rather than a reminder that we still have work to do.

Stem Cell Agency Board Invests in 19 Discovery Research Programs Targeting Cancers, Heart Disease and Other Disorders

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Dr. Judy Shizuru, Stanford University

While stem cell and gene therapy research has advanced dramatically in recent years, there are still many unknowns and many questions remaining about how best to use these approaches in developing therapies. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) today approved investing almost $25 million in 19 projects in early stage or Discovery research.

The awards are from CIRM’s DISC2 Quest program, which supports  the discovery of promising new stem cell-based and gene therapy technologies that could be translated to enable broad use and ultimately, improve patient care.

“Every therapy that helps save lives or change lives begins with a researcher asking a simple question, “What if?”, says Dr. Maria T. Millan, the President and CEO of CIRM. “Our Quest awards reflect the need to keep supporting early stage research, to gain a deeper understanding of stem cells work and how we can best tap into that potential to advance the field.”

Dr. Judy Shizuru at Stanford University was awarded $1.34 million to develop a safer, less-toxic form of bone marrow or hematopoietic stem cell transplant (HCT). HCT is the only proven cure for many forms of blood disorders that affect people of all ages, sexes, and races worldwide. However, current methods involve the use of chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. This approach is toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.

Dr. Shizuru proposes developing an antibody that can direct the patient’s own immune cells to kill diseased blood stem cells. This would make stem cell transplant safer and more effective for the treatment of many life-threatening blood disorders, and more accessible for people in rural or remote parts of the country.

Lili Yang UCLA Broad Stem Cell Research Center: Photo courtesy Reed Hutchinson PhotoGraphics

Dr. Lili Yang at UCLA was awarded $1.4 million to develop an off-the-shelf cell therapy for ovarian cancer, which causes more deaths than any other cancer of the female reproductive system.

Dr. Yang is using immune system cells, called invariant natural killer T cells (iNKT) to attack cancer cells. However, these iNKT cells are only found in small numbers in the blood so current approaches involve taking those cells from the patient and, in the lab, modifying them to increase their numbers and strength before transplanting them back into the patient. This is both time consuming and expensive, and the patient’s own iNKT cells may have been damaged by the cancer, reducing the likelihood of success.

In this new study Dr. Yang will use healthy donor cord blood cells and, through genetic engineering, turn them into the specific form of iNKT cell therapy targeting ovarian cancer. This DISC2 award will support the development of these cells and do the necessary testing and studies to advance it to the translational stage.

Timothy Hoey and Tenaya Therapeutics Inc. have been awarded $1.2 million to test a gene therapy approach to replace heart cells damaged by a heart attack.

Heart disease is the leading cause of death in the U.S. with the highest incidence among African Americans. It’s caused by damage or death of functional heart muscle cells, usually due to heart attack. Because these heart muscle cells are unable to regenerate the damage is permanent. Dr. Hoey’s team is developing a gene therapy that can be injected into patients and turn their cardiac fibroblasts, cells that can contribute to scar tissue, into functioning heart muscle cells, replacing those damaged by the heart attack.

The full list of DISC2 Quest awards is:

APPLICATION NUMBERTITLE OF PROGRAMPRINCIPAL INVESTIGATORAMOUNT
  DISC2-13400  Targeted Immunotherapy-Based Blood Stem Cell Transplantation    Judy Shizuru, Stanford Universtiy  $1,341,910    
  DISC2-13505  Combating Ovarian Cancer Using Stem Cell-Engineered Off-The-Shelf CAR-iNKT Cells    Lili Yang, UCLA  $1,404,000
  DISC2-13515  A treatment for Rett syndrome using glial-restricted
neural progenitor cells  
  Alysson Muotri, UC San Diego  $1,402,240    
  DISC2-13454  Targeting pancreatic cancer stem cells with DDR1 antibodies.    Michael Karin, UC San Diego  $1,425,600  
  DISC2-13483  Enabling non-genetic activity-driven maturation of iPSC-derived neurons    Alex Savtchenko, Nanotools Bioscience  $675,000
  DISC2-13405  Hematopoietic Stem Cell Gene Therapy for Alpha
Thalassemia  
  Don Kohn, UCLA    $1,323,007  
    DISC2-13507  CAR T cells targeting abnormal N-glycans for the
treatment of refractory/metastatic solid cancers  
  Michael Demetriou, UC Irvine  $1,414,800  
  DISC2-13463  Drug Development of Inhibitors of Inflammation Using
Human iPSC-Derived Microglia (hiMG)  
  Stuart Lipton, Scripps Research Inst.  $1,658,123  
  DISC2-13390  Cardiac Reprogramming Gene Therapy for Post-Myocardial Infarction Heart Failure    Timothy Hoey, Tenaya Therapeutics  $1,215,000  
  DISC2-13417  AAV-dCas9 Epigenetic Editing for CDKL5 Deficiency Disorder    Kyle Fink, UC Davis  $1,429,378  
  DISC2-13415  Defining the Optimal Gene Therapy Approach of
Human Hematopoietic Stem Cells for the Treatment of
Dedicator of Cytokinesis 8 (DOCK8) Deficiency  
  Caroline Kuo, UCLA  $1,386,232  
  DISC2-13498  Bioengineering human stem cell-derived beta cell
organoids to monitor cell health in real time and improve therapeutic outcomes in patients  
  Katy Digovich, Minutia, Inc.  $1,198,550  
  DISC2-13469  Novel antisense therapy to treat genetic forms of
neurodevelopmental disease.  
  Joseph Gleeson, UC San Diego  $1,180,654  
  DISC2-13428  Therapeutics to overcome the differentiation roadblock in Myelodysplastic Syndrome (MDS)    Michael Bollong, Scripps Research Inst.  $1,244,160  
  DISC2-13456  Novel methods to eliminate cancer stem cells    Dinesh Rao, UCLA  $1,384,347  
  DISC2-13441  A new precision medicine based iPSC-derived model to study personalized intestinal fibrosis treatments in
pediatric patients with Crohn’s diseas  
  Robert Barrett Cedars-Sinai  $776,340
  DISC2-13512  Modified RNA-Based Gene Therapy for Cardiac
Regeneration Through Cardiomyocyte Proliferation
  Deepak Srivastava, Gladstone Institutes  $1,565,784
  DISC2-13510  An hematopoietic stem-cell-based approach to treat HIV employing CAR-T cells and anti-HIV broadly
neutralizing antibodies  
  Brian Lawson, The Scintillon Institute  $1,143,600  
  DISC2-13475  Developing gene therapy for dominant optic atrophy using human pluripotent stem cell-derived retinal organoid disease model    Xian-Jie Yang, UCLA  $1,345,691  

Can regenerative medicine turn back the clock on aging?

One of my favorite phrases is “standing room only”. I got a chance to use it last week when we held a panel discussion on whether regenerative medicine could turn back the clock on aging. The event was at the annual conference of the International Society for Stem Cell Research (ISSCR) and more than 150 people packed into a conference room to hear the debate (so far more than 800 also watched a live stream of the event.)

It’s not surprising the place was jammed. The speakers included:

  • Dr. Deepak Srivastava, the President of the Gladstone Institutes, an expert on heart disease and the former President of ISSCR.
  • Dr. Stanley “Tom” Carmichael, Chair of the Department of Neurology at UCLA and an expert on strokes and other forms of brain injury.
  • Adrienne Shapiro, the mother of a daughter with sickle cell disease, a tireless patient advocate and supporter of regenerative medicine research, and the co-founder of Axis Advocacy, a family support organization for people with sickle cell.
  • Jonathan Tomas, PhD, JD, the Chair of the CIRM Board.

And the topic is a timely one. It is estimated that as many as 90 percent of the people who die every day, die from diseases of aging such as heart disease, stroke, and cancer. So, what can be done to change that, to not just slow down or stop these diseases, but to turn back the clock, to repair the damage already done and replace cells and tissues already destroyed.

The conversation was enlightening, hopeful and encouraging, but also cautionary.

You can watch the whole event on our Youtube channel.

I think you are going to enjoy it.

How two women are fighting back against Lou Gehrig’s disease

THIS BLOG IS ALSO AVAILABLE AS AN AUDIO CAST

Mary Ann Wittenberg (left) and Nadia Sethi

Lou Gehrig’s disease, or ALS, is a nasty degenerative condition that destroys the brain cells controlling movement. People with ALS suffer a progressive loss of ability to walk, talk, eat and breathe.

The average life expectancy for someone diagnosed with ALS is just two to five years. It has a devastating impact on the people diagnosed and their families.

On the latest episode of our podcast, Talking ‘Bout (re)Generation, we talk to two women who have suffered a loss in this fight, but who are using their experience with ALS to help others battling the disease.

Nadia Sethi became the Director of Community Engagement and Outreach at the ALS Therapy Development Institute after losing her husband to ALS. 

Mary Ann Wittenberg’s husband Harry fought the disease in a public way, starting a blog called “Welcome to My World, How Life Has Changed and Making it Work.” Mary Ann is now carrying on that mission of demystifying the disease.

Their courage and determination to turn a tragedy into something positive, to help others, and to hopefully play a role in finding treatments to help people with ALS, is deeply moving and inspiring.

We hope you enjoy this special episode of ‘Talking ‘Bout (re)Generation’.

CIRM has invested more than $92 million in 33 different projects targeting ALS. You can read about them on our ALS Fact Sheet.

CIRM CNS Consortium Workshop – Held Feb. 24 & 25, 2022

Note: Post edited to include post-event workshop videos. Watch both workshop videos here and here.

THIS BLOG IS ALSO AVAILABLE AS AN AUDIO CAST

Shared Stem Cell Laboratory at UCLA

Advance World Class Science, Deliver Real World Solutions, Provide Opportunity for All. 

These comprise the themes of our bold 5-year Strategic Plan. Since its launch less than two months ago, we have hit the ground running. Under the second and third strategic themes, we have already received ICOC approval for 2 concepts: Alpha Clinics Network Expansion and COMPASS educational program. We are now working on the execution of our first theme.  

As indicated in our Strategic Plan, we strongly believe advancing world class science relies on collaborative research that leverages collective scientific knowledge. To that end, we have organized the virtual CIRM CNS Consortium Workshop (click for the agenda and see registration details below) to help us gather feedback from a panel of experts about the best approach for promoting a culture of collaboration.

The vision for this workshop was informed by multiple layers of stakeholder discussions and input that started even prior to the passage of Proposition 14. A quick walk down memory lane reminds us of CIRM’s early and deliberate effort to identify areas of opportunity for promoting a paradigm shift with a “team science” approach, especially in the context of complex diseases such as those affecting the CNS: 

  • In 2019, we organized Brainstorming Neurodegeneration, a workshop where broad stakeholder input was received about the benefits and bottlenecks of developing a consortium approach where genomics and big data, novel stem cell models, and patient data could be collectively leveraged to advance the field of neurodegenerative research in a collaborative manner.  
  • In 2020, just before the passage of Prop 14 and based on input from the 2019 workshop, we already had our eyes on target: the future of collaborative research is in sharable data, and sharing petabytes or more of data requires a collaborative data infrastructure. To better understand the status and bottlenecks of knowledge platforms that could leverage data sharing, we brought together a panel of experts at our 2020 Grantee Meeting. We were encouraged to learn that our laser-focused approach for promoting knowledge sharing was right on target and the panelists suggested that CIRM has a great opportunity to promote a paradigm shift in this area.   
  • In early 2021, immediately after the passage of Prop 14 and building upon our previous conversations, we formed a Strategic Scientific Advisory Panel comprising a distinguished group of national and international scientists in the stem cell field. Once again, we were advised to expand sharable resources (especially in the context of stem cell modeling), bring more attention to complex diseases such as neurodegenerative and neuropsychiatric disorders, and facilitate knowledge sharing.  
  • In mid 2021, as we were forming our Strategic Plan based on the above input, we pressure-tested our paradigm-shifting vision in a Town Hall and further gathered feedback from California stakeholders about their needs. Again, all arrows pointed to shared resources and data as critical elements for accelerating research.  
CIRM Town Hall workshop hosted in 2021
  • Finally, in late 2021, just before the launch of our Strategic Plan, we organized a Data Biosphere Advisory Committee to advise us on ways to facilitate collaborative knowledge sharing. Here, we explored various models for leveraging and/or generating a data infrastructure in which CIRM-funded data could be managed and shared. The main outcome of this meeting was a recommendation to organize a workshop to test the feasibility and approach for generation of a CIRM knowledge platform. The Committee concluded that CIRM is uniquely positioned to contribute a wealth of data to the broader scientific community. A knowledge platform would provide an avenue for data sharing and collaboration with other groups that are dedicated to accelerating progress in the development of therapies, especially for CNS disorders.  

We were walking on solid ground! In December of 2021, paralleling the input we had received from experts and stakeholders, we launched our 5-year Strategic Plan with the goal of advancing world class science by promoting a culture of collaboration. 

To deliver on this goal, CIRM’s approach is to build the infrastructure (and we don’t mean bricks and mortar) that organizes and democratizes data through:  

  1. A network of shared resources labs that facilitate validation and standardization to support California regenerative medicine researchers  
  1. A data infrastructure where CIRM-funded data can be shared and external datasets leveraged to maximize real-world impact  
  1. We have held a virtual CNS Consortium Workshop on February 24th and 25th where we explored the development of these two resources through the deployment of a consortium and starting in the CNS space as a use case. While the discussions at the workshop centered on the CNS, the shared resources labs will be implemented across cell types and organs. The Data Infrastructure is intended to be a global resource for data sharing and fostering a culture of open science for all CIRM grantees—and the world. The complete workshop agenda can be found here.  

    Watch video recordings of Day 1 and Day 2 of the CNS workshop.