Three families battling a life-threatening immune disorder got some great news last week. A clinical trial that could save the life of their child has once again been given the go-ahead by the US Food and Drug Administration (FDA).
The clinical trial is the work of UCLA’s Dr. Don Kohn, and was strongly supported by CIRM. It is targeting ADA-SCID, a condition where the child is born without a functioning immune system so even a simple infection could prove fatal. In the past they were called “bubble babies” because some had been placed inside sterile plastic bubbles to protect them from germs.
Dr. Kohn’s approach – using the patient’s own blood stem cells, modified in the lab to correct the genetic mutation that causes the problem – had shown itself to be amazingly effective. In a study in the prestigious New England Journal of Medicine, the researchers showed that of 50 patients treated all had done well and 97 percent were considered cured.
UCLA licensed the therapy to Orchard Therapeutics, who planned to complete the testing needed to apply for permission to make it more widely available. But Orchard ran into problems and shelved the therapy.
After lengthy negotiations Orchard returned the therapy to UCLA last year and now the FDA has given clearance for UCLA to resume treating patients. That is expected to start early next year using CIRM funds left over when Orchard halted its work.
One of the people who played a big role in helping persuade Orchard to return the therapy to UCLA is Alysia Vaccaro. She is the mother of Evie, a child born with ADA-SCID who was cured by Dr. Kohn and his team and is now a thriving 9 year old.
You can watch an interview we did with Alysia about the impact this research has had on her family, and how important it is for other families with ADA-SCID kids.
Now there’s more encouraging news from a CIRM-funded clinical trial with Jasper Therapeutics. They have announced that they have tested their approach in 16 patients, with encouraging results and no serious adverse events.
Let’s back up a little. Children born with SCID have no functioning immune system, so even a simple infection can prove life threatening. Left untreated, children with SCID often die in the first few years of life. Several of the approaches CIRM has funded use the child’s own blood stem cells to help fix the problem. But at Jasper Therapeutics they are using another approach. They use a bone marrow or hematopoietic stem cell transplant (HCT). This replaces the child’s own blood supply with one that is free of the SCID mutation, which helps restore their immune system.
However, there’s a problem. Most bone marrow transplants use chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. It can be effective, but it is also toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.
To get around that problem Jasper Therapeutics is using an antibody called JSP191 – developed with CIRM funding – that directs the patient’s own immune cells to kill diseased blood stem cells, creating room to transplant new, healthy cells. To date the therapy has already been tested in 16 SCID patients.
In addition to treating 16 patients treated without any apparent problems, Jasper has also been granted Fast Track Designation by the US Food and Drug Administration. This can help speed up the review of treatments that target serious unmet conditions. They’ve also been granted both Orphan and Rare Pediatric Disease designations. Orphan drug designation qualifies sponsors for incentives such as tax credits for clinical trials. Rare Pediatric Disease designation means that if the FDA does eventually approve JSP191, then Jasper can apply to receive a priority review of an application to use the product for a different disease, such as someone who is getting a bone marrow transplant for sickle cell disease or severe auto immune diseases.
In a news release, Ronald Martell, President and CEO of Jasper Therapeutics said:
“The FDA’s Fast Track designation granted for JSP191 in Severe Combined Immunodeficiency (SCID) reinforces the large unmet medical need for patients with this serious disease. Along with its previous designations of Orphan and Rare Pediatric Disease for JSP191, the FDA’s Fast Track recognizes JSP191’s potential role in improving clinical outcomes for SCID patients, many of whom are too fragile to tolerate the toxic chemotherapy doses typically used in a transplant.”
I’ve always been impressed by the willingness of individuals to step forward and volunteer for a clinical trial. Even more so when they are the first person ever to test a first-in-human therapy. They really are pioneers in helping advance a whole new approach to treating disease.
That’s certainly the case for the first individual treated in a CIRM-funded clinical trial to develop a functional cure for HIV/AIDS. Caring Cross announced recently that they have dosed the first patient in the trial testing their anti-HIV duoCAR-T cell therapy.
The trial is being led by UC San Francisco’s Dr. Steven Deeks and UC Davis’ Dr. Mehrdad Abedi. Their approach involves taking a patient’s own blood and extracting T cells, a type of immune cell. The T cells are then genetically modified to express two different chimeric antigen receptors (CAR), which enable the newly created duoCAR-T cells to recognize and destroy HIV infected cells. The modified T cells are then reintroduced back into the patient.
The goal of this one-time therapy is to act as a long-term control of HIV with patients no longer needing to take anti-HIV medications. If it is successful it would be, in effect, a form of functional HIV cure.
This first phase involves giving different patients different levels of the duoCAR-T therapy to determine the best dose, and to make sure it is safe and doesn’t cause any negative side effects.
This is obviously just the first step in a long process, but it’s an important first step and certainly one worth marking. As Dr. Deeks said in the news release, “We have reached an important milestone with the dosing of the first participant in the Phase 1/2a clinical trial evaluating a potentially groundbreaking anti-HIV duoCAR-T cell therapy. Our primary goal for this clinical trial is to establish the safety of this promising therapeutic approach.”
Dr. Abedi, echoed that saying. “The first participant was dosed with anti-HIV duoCAR-T cells at the UC Davis medical center in mid-August. There were no adverse events observed that were related to the product and the participant is doing fine.”
This approach carries a lot of significance not just for people with HIV in the US, but also globally. If successful it could help address the needs of people who are not able to access antiretroviral therapies or for whom those medications are no longer effective.
Today there are an estimated 38 million people living with HIV around the world. Every year some 650,000 people die from the disease.
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.
The use of antiretroviral drugs has turned HIV/AIDS from a fatal disease to one that can, in many cases in the US, be controlled. But these drugs are not a cure. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) voted to approve investing $6.85 million in a therapy that aims to cure the disease.
This is the 82nd clinical trial funded by CIRM.
There are approximately 38 million people worldwide living with HIV/AIDS. And each year there are an estimated 1.5 million new cases. The vast majority of those living with HIV do not have access to the life-saving antiretroviral medications that can keep the virus under control. People who do have access to the medications face long-term complications from them including heart disease, bone, liver and kidney problems, and changes in metabolism.
The antiretroviral medications are effective at reducing the viral load in people with HIV, but they don’t eliminate it. That’s because the virus that causes AIDS can integrate its DNA into long-living cells in the body and remain dormant. When people stop taking their medications the virus is able to rekindle and spread throughout the body.
Dr. William Kennedy and the team at Excision Bio Therapeutics have developed a therapeutic candidate called EBT-101. This is the first clinical study using the CRISPR-based platform for genome editing and excision of the latent form of HIV-1, the most common form of the virus that causes AIDS in the US and Europe. The goal is to eliminate or sufficiently reduce the hidden reservoirs of virus in the body to the point where the individual is effectively cured.
“To date only a handful of people have been cured of HIV/AIDS, so this proposal of using gene editing to eliminate the virus could be transformative,” says Dr. Maria Millan, President and CEO of CIRM. “In California alone there are almost 140,000 people living with HIV. HIV infection continues to disproportionately impact marginalized populations, many of whom are unable to access the medications that keep the virus under control. A functional cure for HIV would have an enormous impact on these communities, and others around the world.”
In a news release announcing they had dosed the first patient, Daniel Dornbusch, CEO of Excision, called it a landmark moment. “It is the first time a CRISPR-based therapy targeting an infectious disease has been administered to a patient and is expected to enable the first ever clinical assessment of a multiplexed, in vivo gene editing approach. We were able to reach this watershed moment thanks to years of innovative work by leading scientists and physicians, to whom we are immensely grateful. With this achievement, Excision has taken a major step forward in developing a one-time treatment that could transform the HIV pandemic by freeing affected people from life-long disease management and the stigma of disease.”
The Excision Bio Therapeutics team also scored high on their plan for Diversity, Equity and Inclusion. Reviewers praised them for adding on a partnering organization to provide commitments to serve underserved populations, and to engaging a community advisory board to help guide their patient recruitment.
For children born with severe combined immunodeficiency (SCID) life can be very challenging. SCID means they have no functioning immune system, so even a simple infection can prove life threatening. Left untreated, children with SCID often die in the first few years of life.
There are stem cell/gene therapies funded by the California Institute for Regenerative Medicine (CIRM), such as ones at UCLA and UCSF/St. Judes, but an alternative method of treating, and even curing the condition, is a bone marrow or hematopoietic stem cell transplant (HCT). This replaces the child’s blood supply with one that is free of the SCID mutation, which helps restore their immune system.
However, current HCT 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.
To change that, Dr. Judy Shizuru at Stanford University, with CIRM funding, developed an antibody that can direct the patient’s own immune cells to kill diseased blood stem cells, creating the room needed to transplant new, healthy cells. The goal was to make stem cell transplants safer and more effective for the treatment of many life-threatening blood disorders.
That approach, JSP191, is now being championed by Jasper Therapeutics and they just got some very good news from the Food and Drug Administration (FDA). The FDA has granted JSP191 Fast Track Designation, which can speed up the review of therapies designed to treat serious conditions and fill unmet medical needs.
In a news release, Ronald Martell, President and CEO of Jasper Therapeutics, said this is good news for the company and patients: “This new Fast Track designation recognizes the potential role of JSP191 in improving clinical outcomes for these patients and will allow us to more closely work with the FDA in the upcoming months to determine a path toward a Biologics License Application (BLA) submission.”
Getting a BLA means Jasper will be able to market the antibody in the US and make it available to all those who need it.
This is the third boost from the FDA for Jasper. Previously the agency granted JSP191 both Orphan and Rare Pediatric Disease designations. Orphan drug designation qualifies sponsors for incentives such as tax credits for clinical trials. Rare Pediatric Disease designation means that if the FDA does eventually approve JSP191, then Jasper can apply to receive a priority review of an application to use the product for a different disease, such as someone who is getting a bone marrow transplant for sickle cell disease or severe auto immune diseases.
September is National Sickle Cell Awareness Month, a time to refocus our efforts to find new treatments, even a cure, for people with sickle cell disease. Until we get those, CIRM remains committed to doing everything we can to reduce the stigma and bias that surrounds it.
Sickle cell disease (SCD) is a rare, inherited blood disorder in which normally smooth and round red blood cells may become sickle-shaped and harden. These blood cells can clump together and clog up arteries, causing severe and unpredictable bouts of pain, organ damage, vision loss and blindness, strokes and premature death.
There is a cure, a bone marrow transplant from someone who is both a perfect match and doesn’t carry the SCD trait. However, few patients are able to find that perfect match and even if they do the procedure carries risks.
The GRASP Trial is a Phase 2 trial that will take place at various locations throughout the country. It’s a collaboration between the NHLBI and CIRM. Researchers are testing whether a gene therapy approach can improve or eliminate sickle cell pain episodes.
Shortly after being born, babies stop producing blood containing oxygen-rich fetal hemoglobin and instead produce blood with the adult hemoglobin protein. For children with sickle cell disease, the transition from the fetal to the adult form of hemoglobin marks the onset of anemia and the painful symptoms of the disorder.
Scientists previously discovered that the BCL11A gene helps to control fetal hemoglobin and that decreasing the expression of this gene can increase the amount of fetal hemoglobin while at the same time reducing the amount of sickle hemoglobin in blood. This could result in boosting the production of normal shaped red blood cells with a goal of curing or reducing the severity of sickle cell disease.
The approach used in this trial is similar to a bone marrow transplant, but instead of using donor stem cells, this uses the patient’s own blood stem cells with new genetic information that instructs red blood cells to silence the expression of the BCL11A gene. This approach is still being studied to make sure that it is safe and effective, but it potentially has the advantage of eliminating some of the risks of other therapies.
In this trial, patients will have to spend some time in an inpatient unit as they undergo chemotherapy to kill some bone marrow blood stem cells and create room for the new, gene-modified cells to take root.
The trial is based on a successful pilot/phase 1 study which showed it to be both safe and effective in the initial 10 patients enrolled in the trial.
For more information about the trial, including inclusion/exclusion criteria and trial locations, please visit the CureSCi GRASP trial page.
Nancy Rene, a sickle cell disease patient advocate, says while clinical trials like this are obviously important, there’s another aspect of the treatment of people with the disease that is still too often overlooked.
“As much as I applaud CIRM for the work they are doing to find a therapy or cure for Sickle Cell, I am often dismayed by the huge gulf between research protocols and general medical practice. For every story I hear about promising research, there is often another sad tale about a sickle cell patient receiving inadequate care. This shouldn’t be an either/or proposition. Let’s continue to support ground-breaking research while we expand education and training for medical professionals in evidenced based treatment. I look forward to the day when sickle cell patients receive the kind of treatment they need to lead healthy, pain-free lives.”
An ever-growing array of academic and industry resources are required to rapidly translate scientific discoveries and emerging technologies toward safe and effective regenerative medicine therapies for patients. To help, the California Institute for Regenerative Medicine (CIRM) is creating a network of Industry Resource Partners (IRP) that will make its unique resources available to help accelerate the progression of CIRM-funded Discovery, Translational and Clinical stage research projects toward transformative regenerative medicine therapies for rare and prevalent diseases.
The Industry Resource Partners will offer their services, technologies and expertise to CIRM-funded projects in a cost-effective, stage-appropriate and consistent manner.
For example, Novo Nordisk is making research-grade vials of its Good Manufacturing Practice (GMP)-grade human embryonic stem cell line available for CIRM Discovery Quest stage research projects at no cost. Having access to clinically compatible pluripotent stem cell lines such as this one will help CIRM researchers accelerate the translation of their therapeutic discoveries toward clinical use. Researchers will also have future access to Novo Nordisk’s GMP seed stock as well as opportunities for partnering with Novo Nordisk.
“CIRM is a lender of first resort, supporting projects in the very early stages, long before they are able to attract outside investment,” says Shyam Patel, PhD, the Director of Business Development at CIRM. “With the launch of this program we hope to create a force-multiplier effect by bringing in industry partners who have the resources, experience and expertise to help further accelerate CIRM-funded regenerative medicine research projects.”
This new network builds on work CIRM started in 2018 with the Industry Alliance Program (IAP). The goal of the IAP was to partner researchers and industry to help accelerate the most promising stem cell, gene and regenerative medicine therapy programs to commercialization. Four of the members of the IAP are also founding members or the IRP.
In addition to Novo Nordisk, the IRP includes:
ElevateBio is providing access to high quality, well-characterized induced pluripotent stem cell (iPSC) lines to CIRM Discovery Quest stage research projects for product development in regenerative medicine. CIRM awardees will also have access to ElevateBio’s viral vector technologies, process development, analytical development, and GMP manufacturing services.
Bayer is offering to support the cell therapy process development and GMP manufacturing needs of CIRM Translational and Clinical awardees at its newly built Berkeley facilities. The partnered projects will have access to Bayer’s cell therapy manufacturing facilities, equipment, resources and expertise. Bayer is also open to partnering from fee-based-services to full business development and licensing opportunities.
Resilience is providing access to its GMP manufacturing services for CIRM Translational and Clinical Stage projects. In addition to providing access to its cell therapy manufacturing services and partnering opportunities, Resilience will provide project consultation that could aid CIRM applicants in drafting manufacturing plans and budgets for CIRM applications.
“These partnerships are an important step forward in helping advance not only individual projects but also the field as a whole,” says Dr. Maria T. Millan, President and CEO of CIRM. “One of the biggest challenges facing regenerative medicine right now involves manufacturing. Providing researchers with access to high quality starting materials and advanced manufacturing capabilities is going to be essential in helping these projects maintain high quality standards and comply with the regulatory frameworks needed to bring these therapies to patients.”
While the IRP Network will offer its services to CIRM grantees there is no obligation or requirement that any CIRM awardee take advantage of these services.
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 Program2022
Despite advances in treatments in recent years heart disease remains the leading cause of death in the US. It accounts for one in three deaths in this country, and many people are not even aware they have a problem until they have a heart attack.
One of the early warning signs of danger is a heart arrhythmia; that’s when electrical signals that control the hearts beating don’t work properly and can result in the heart beating too fast, too slow, or irregularly. However, predicting who is at risk of these arrhythmias is difficult. Now new research may have found a way to change that.
A research team at the Institute of Molecular and Cell Biology in Singapore combined stem cells with machine learning, and developed a way to predict arrhythmias, with a high degree of accuracy.
The team used stem cells to create different batches of cardiomyocytes or heart muscle cells. Some of these batches were healthy heart cells, but some had arrhythmias caused by different problems such as a genetic disorder or drug induced.
They then trained a machine learning program to use videos to scan the 3,000 different groups of cells. By studying the different beating patterns of the cells, and then using the levels of calcium in the cells, the machine was able to predict, with 90 percent accuracy, which cells were most likely to experience arrhythmias.
The researchers say their approach is faster, simpler and more accurate than current methods of trying to predict who is at risk for arrhythmias and could have a big impact on our ability to intervene before the individual suffers a fatal heart attack.
The California Institute for Regenerative Medicine has invested more than $180 million in more than 80 different projects, including four clinical trials, targeting heart disease.
The Stem Cellar 