Unlocking a key behind why our bones get weaker as we age

Magnified image of a bone with osteoporosis. Photo Courtesy Sciencephoto.com

Getting older brings with it a mixed bag of items. If you are lucky you can get wiser. If you are not so lucky you can get osteoporosis. But while scientists don’t know how to make you wiser, they have gained some new insights into what makes bones weak and so they might be able to help with the osteoporosis.

Around 200 million people worldwide suffer from osteoporosis, a disease that causes bones to become so brittle that in extreme cases even coughing can lead to a fracture.

Scientists have known for some time that the cells that form the building blocks of our skeletons are found in the bone marrow. They are called mesenchymal stem cells (MSCs) and they have the ability to turn into a number of different kinds of cells, including bone or fat. The keys to deciding which direction the MSCs take are things called epigenetic factors, these basically control which genes are switched on or off and in what order. Now researchers from the UCLA School of Dentistry have identified an enzyme that plays a critical role in that process.

The team found that when the enzyme KDM4B is missing in MSCs those cells are more likely to become fat cells rather than bone cells. Over time that leads to weaker bones and more fractures.

In a news release Dr. Cun-Yu Wang, the lead researcher, said: “We know that bone loss comes with age, but the mechanisms behind extreme cases such as osteoporosis have, up until recently, been very vague.”

To see if they were on the right track the team created a mouse model that lacked KDM4B. Just as they predicted the MSCs in the mouse created more fat than bone, leading to weaker skeletons.

They also looked at mice who were placed on a high fat diet – something known to increase bone loss and weaker bones in people – and found that the diet seemed to reduce KDM4B which in turn produced weaker bones.

In the news release Dr. Paul Krebsbach, Dean of the UCLA School of Dentistry, said the implications for the research are enormous. “The work of Dr. Wang, his lab members and collaborators provides new molecular insight into the changes associated with skeletal aging. These findings are an important step towards what may lead to more effective treatment for the millions of people who suffer from bone loss and osteoporosis.”

The study is published in the journal Cell Stem Cell.

Surviving with Joy

Dr. Tippi MacKenzie (left) of UCSF Benioff Children’s Hospital San Francisco, visits with newborn Elianna and parents Nichelle Obar and Chris Constantino. Photo by Noah Berger

Alpha thalassemia major is, by any stretch of the imagination, a dreadful, heart breaker of a disease. It’s caused by four missing or mutated genes and it almost always leads to a fetus dying before delivery or shortly after birth. Treatments are limited and in the past many parents were told that all they can do is prepare for the worst.

Now, however, there is new hope with new approaches, including one supported by CIRM, helping keep these children alive and giving them a chance at a normal life.

Thalassemias are a group of blood disorders that affect the way the body makes hemoglobin, which helps in carrying oxygen throughout the body. In alpha thalassemia major it’s the lack of alpha globin, a key part of hemoglobin, that causes the problem. Current treatment requires in blood transfusions to the fetus while it is still in the womb, and monthly blood transfusions for life after delivery, or a bone marrow transplant if a suitable donor is identified.

A clinical trial run by University of California San Francisco’s Dr. Tippi MacKenzie – funded by CIRM – is using a slightly different approach. The team takes stem cells from the mother’s bone marrow and then infuses them into the fetus. If accepted by the baby’s bone marrow, these stem cells can then mature into healthy blood cells. The hope is that one day this method will enable children to be born with a healthy blood supply and not need regular transfusions.

Treating these babies, saving their lives, is the focus of a short film from UCSF called “Surviving with Joy”. It’s a testament to the power of medicine, and the courage and resilience of parents who never stopped looking for a way to help their child.

Tissues are optional but advised.

DNA therapeutic treats blood cancer in mice and begins human clinical trial

The left image represents a microscopic view of the bone marrow of a myeloma-bearing mouse treated with control, and the right image represents the same for a myeloma-bearing mouse treated with ION251, an experimental therapeutic. The red dots represent the IRF4 protein within human myeloma cells, which are much sparser after ION251 treatment. Image credit: UC San Diego Health

Multiple myeloma is the second most common blood cancer in the United States, with more than 32,000 new cases predicted in 2020.  Unfortunately, many patients with this type of blood cancer eventually develop resistance to multiple types of treatments.  This phenomenon is partially due to the fact that cancer stem cells, which have the ability to evade traditional therapies and then self-renew, help drive the disease.

It is for this reason that a team of researchers, at the UC San Diego School of Medicine and Ionis Pharmaceuticals, are developing a therapy that can destroy these malignant stem cells, thereby preventing the cancer from coming back.  With support from CIRM, the team developed an approach that interacts with IRF4, a gene that allows myeloma stem cells and tumor cells to grow and survive chemotherapy and radiation.  They have engineered an oligonucleotide, a short DNA molecule, to prevent IRF4 from functioning.  The therapy, known as ION251, lowered disease burden, reduced the amount of myeloma stem cells, and increased survival when tested in mice bearing human myeloma.  These results have enabled the team to start a Phase I clinical trial to see if this approach is safe and effective in people with myeloma.

To study the disease and test ION251, the team transplanted human myeloma cells into mice that lack an immune system and thus won’t reject human cells.  Ten mice received the ION251 treatment and an additional ten mice received a control treatment.  After receiving the ION251 therapy, the treated mice had significantly fewer myeloma cells after two to six weeks of treatment.  Additionally, 70 to 100 percent of the treated mice survived, whereas none of the untreated control mice did. 

In a news release from UC San Diego Health, Dr. Leslie Crews, co-senior author and assistant professor at the UCSD School of Medicine, elaborated on the promising results from the mouse study.

“The results of these preclinical studies were so striking that half the microscopy images we took to compare bone marrow samples between treated and untreated mice kept coming back blank — in the treated mice, we couldn’t find any myeloma cells left for us to study.  It makes the science more difficult, but it gives me hope for patients.”

The Phase I clinical trial to assess the safety of ION251, sponsored by Ionis Pharmaceuticals, is now recruiting participants at Moores Cancer Center at UC San Diego Health and elsewhere. More information on this can be viewed by clicking the link here.

The full results of this study were published in the journal Cell Stem Cell.

CIRM-funded therapy to ease the impact of chemotherapy

Treatments for cancer have advanced a lot in recent years, but many still rely on the use of chemotherapy to either shrink tumors before surgery or help remove cancerous cells the surgery missed. The chemo can be very effective, but it’s also very toxic. Angiocrine Bioscience Inc. is developing a way to reduce those toxic side effects, and they just got a nice vote of confidence for that approach.

The US Food and Drug Administration (FDA) has granted Angiocrine Regenerative Medicine Advanced Therapy (RMAT) designation for their product AB-205.

RMAT is a big deal. It means the therapy, in this case AB-205, has already shown it is safe and potentially beneficial to patients, so the designation means that if it continues to be safe and effective it may be eligible for a faster, more streamlined approval process. And that means it can get to the patients who need it, outside of a clinical trial, faster.

What is AB-205? Well it’s made from genetically engineered cells, derived from cord blood, designed to help alleviate or accelerate recovery from the toxic side effects of chemotherapy for people undergoing treatment for lymphoma and other aggressive cancers of the blood or lymph system.

CIRM awarded Angiocrine Bioscience $6.2 million in 2018 to help carry out the Phase 2 clinical trial testing the therapy. In a news release ,CIRM President & CEO, Dr. Maria Millan, said there is a real need for this kind of therapy.

“This is a project that CIRM has supported from an earlier stage of research, highlighting our commitment to moving the most promising research out of the lab and into people. Lymphoma is the most common blood cancer and the 6th most commonly diagnosed cancer in California. Despite advances in therapy many patients still suffer severe complications from the chemotherapy, so any treatment that can reduce those complications can not only improve quality of life but also, we hope, improve long term health outcomes for patients.”

In a news release Dr. Paul Finnegan, Angiocrine’s CEO, welcomed the news.

“The RMAT designation speaks to the clinical meaningfulness and the promising efficacy data and safety profile of AB-205 based on our Phase 1b/2 study. This is an important step in accelerating the development of AB-205 towards its first market approval. We appreciate the thorough assessment provided by the FDA reviewers and the support from our partner, the California Institute for Regenerative Medicine.” 

The investment in Angiocrine marked a milestone for CIRM. It was the 50th clinical trial we had funded. It was a cause for celebration then. We’re hoping it will be a cause for an even bigger celebration in the not too distant future.

The company hopes to start a Phase 3 clinical trial in the US and Europe next year.

CIRM Board Approves Four New Clinical Trials

A breakdown of CIRM’s clinical trials by disease area

This past Thursday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved four new clinical trials in addition to ten new discovery research awards.

These new awards bring the total number of CIRM-funded clinical trials to 68.  Additionally, these new additions have allowed the state agency to exceed the goal of commencing 50 new trials outlined in its five year strategic plan.

$8,970,732 was awarded to Dr. Steven Deeks at the University of California San Francisco (UCSF) to conduct a clinical trial that modifies a patient’s own immune cells in order to treat and potentially cure HIV. 

Current treatment of HIV involves the use of long-term antiretroviral therapy (ART).  However, many people are not able to access and adhere to long-term ART.

Dr. Deeks and his team will take a patient’s blood and extract 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 ART, in effect a form of HIV cure.  This approach would also address the needs of those who are not able to respond to current approaches, which is estimated to be 50% of those affected by HIV globally. 

$3,728,485 was awarded to Dr. Gayatri Rao from Rocket Pharmaceuticals to conduct a clinical trial using a gene therapy for infantile malignant osteopetrosis (IMO), a rare and life-threatening disorder that develops in infancy.  IMO is caused by defective bone cell function, which results in blindness, deafness, bone marrow failure, and death very early in life. 

The trial will use a gene therapy that targets IMO caused by mutations in the TCIRG1 gene.  The team will take a young child’s own blood stem cells and inserting a functional version of the TCIRG1 gene.  The newly corrected blood stem cells are then introduced back into the child, with the hope of halting or preventing the progression of IMO in young children before much damage can occur. 

Rocket Pharmaceuticals has used the same gene therapy approach for modifying blood stem cells in a separate CIRM funded trial for a rare pediatric disease, which has shown promising results.

$8,996,474 was awarded to Dr. Diana Farmer at UC Davis to conduct a clinical trial of in utero repair of myelomeningocele (MMC), the most severe form of spina bifida.  MMC is a birth defect that occurs due to incomplete closure of the developing spinal cord, resulting in neurological damage to the exposed cord.  This damage leads to lifelong lower body paralysis, and bladder and bowel dysfunction.

Dr. Farmer and her team will use placenta tissue to generate mesenchymal stem cells (MSCs).  The newly generated MSCs will be seeded onto an FDA approved dural graft and the product will be applied to the spinal cord while the infant is still developing in the womb.  The goal of this therapy is to help promote proper spinal cord formation and improve motor function, bladder function, and bowel function. 

The clinical trial builds upon the work of CIRM funded preclinical research.

$8,333,581 was awarded to Dr. David Williams at Boston Children’s Hospital to conduct a gene therapy clinical trial for sickle cell disease (SCD).  This is the second project that is part of an agreement between CIRM and the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, to co-fund cell and gene therapy programs under the NHLBI’s  “Cure Sickle Cell” Initiative.  The goal of this agreement is to markedly accelerate clinical development of cell and gene therapies to cure SCD.

SCD is an inherited disease caused by a single gene mutation resulting in abnormal hemoglobin, which causes red blood cells to ‘sickle’ in shape.  Sickling of red blood cells clogs blood vessels and leads to progressive organ damage, pain crises, reduced quality of life, and early death. 

The team will take a patient’s own blood stem cells and insert a novel engineered gene to silence abnormal hemoglobin and induce normal fetal hemoglobin expression.  The modified blood stem cells will then be reintroduced back into the patient.  The goal of this therapy is to aid in the production of normal shaped red blood cells, thereby reducing the severity of the disease.

“Today is a momentus occasion as CIRM reaches 51 new clinical trials, surpassing one of the goals outlined in its five year strategic plan,” says Maria T. Millan, M.D., President and CEO of CIRM.  “These four new trials, which implement innovative approaches in the field of regenerative medicine, reflect CIRM’s ever expanding and diverse clinical portfolio.”

The Board also approved ten awards that are part of CIRM’s Quest Awards Prgoram (DISC2), which promote promising new technologies that could be translated to enable broad use and improve patient care.

The awards are summarized in the table below:

  APPLICATION  TITLE  INSTITUTION  AWARD AMOUNT  
    DISC2-12169  Human-induced pluripotent stem cell-derived glial enriched progenitors to treat white matter stroke and vascular dementia.  UCLA  $250,000
  DISC2-12170Development of COVID-19 Antiviral Therapy Using Human iPSC-Derived Lung Organoids  UC San Diego  $250,000
  DISC2-12111Hematopoietic Stem Cell Gene Therapy for X-linked Agammaglobulinemia  UCLA  $250,000
  DISC2-12158Development of a SYF2 antisense oligonucleotide (ASO) treatment for ALSUniversity of Southern California  $249,997
    DISC2-12124Dual angiogenic and immunomodulating nanotechnology for subcutaneous stem cell derived islet transplantation for the treatment of diabetes  Lundquist Institute  $250,000
  DISC2-12105Human iPSC-derived chimeric antigen receptor-expressing macrophages for cancer treatment  UC San Diego  $250,000
  DISC2-12164Optimization of a human interneuron cell therapy for traumatic brain injury  UC Irvine  $250,000
  DISC2-12172Combating COVID-19 using human PSC-derived NK cells  City of Hope  $249,998
  DISC2-12126The First Orally Delivered Cell Therapy for the Treatment of Inflammatory Bowel Disease  Vitabolus Inc.  $249,000
    DISC2-12130Transplantation of Pluripotent Stem Cell Derived Microglia for the Treatment of Adult-onset Leukoencephalopathy (HDLS/ALSP)  UC Irvine  $249,968

Cures, clinical trials and unmet medical needs

When you have a great story to tell there’s no shame in repeating it as often as you can. After all, not everyone gets to hear first time around. Or second or third time. So that’s why we wanted to give you another opportunity to tune into some of the great presentations and discussions at our recent CIRM Alpha Stem Cell Clinic Network Symposium.

It was a day of fascinating science, heart-warming, and heart-breaking, stories. A day to celebrate the progress being made and to discuss the challenges that still lie ahead.

There is a wide selection of topics from “Driving Towards a Cure” – which looks at some pioneering work being done in research targeting type 1 diabetes and HIV/AIDS – to Cancer Clinical Trials, that looks at therapies for multiple myeloma, brain cancer and leukemia.

The COVID-19 pandemic also proved the background for two detailed discussions on our funding for projects targeting the coronavirus, and for how the lessons learned from the pandemic can help us be more responsive to the needs of underserved communities.

Here’s the agenda for the day and with each topic there’s a link to the video of the presentation and conversation.

Thursday October 8, 2020

View Recording: CIRM Fellows Trainees

9:00am Welcome Mehrdad Abedi, MD, UC Davis Health, ASCC Program Director  

Catriona Jamieson, MD,  View Recording: ASCC Network Value Proposition

9:10am Session I:  Cures for Rare Diseases Innovation in Action 

Moderator: Mark Walters, MD, UCSF, ASCC Program Director 

Don Kohn, MD, UCLA – View Recording: Severe combined immunodeficiency (SCID) 

Mark Walters, MD, UCSF, ASCC Program Director – View Recording: Thalassemia 

Pawash Priyank, View Recording: Patient Experience – SCID

Olivia and Stacy Stahl, View Recording: Patient Experience – Thalassemia

10 minute panel discussion/Q&A 

BREAK

9:55am Session II: Addressing Unmet Medical Needs: Driving Towards a Cure 

Moderator: John Zaia, MD, City of Hope, ASCC Program Direction 

Mehrdad Abedi, MD, UC Davis Health, ASCC Program Director – View Recording: HIV

Manasi Jaiman, MD, MPH, ViaCyte, Vice President, Clinical Development – View Recording: Diabetes

Jeff Taylor, Patient Experience – HIV

10 minute panel discussion/Q&A 

BREAK

10:40am Session III: Cancer Clinical Trials: Networking for Impact 

Moderator: Catriona Jamieson, MD, UC San Diego, ASCC Program Director 

Daniela Bota, MD, PhD, UC Irvine, ASCC Program Director – View Recording:  Glioblastoma 

Michael Choi, MD, UC San Diego – View Recording: Cirmtuzimab

Matthew Spear, MD, Poseida Therapeutics, Chief Medical Officer – View Recording: Multiple Myeloma  

John Lapham, Patient Experience –  View Recording: Chronic lymphocytic leukemia (CLL) 

10 minute panel discussion/Q&A 

BREAK

11:30am Session IV: Responding to COVID-19 and Engaging Communities

Two live “roundtable conversation” sessions, 1 hour each.

Roundtable 1: Moderator Maria Millan, MD, CIRM 

CIRM’s / ASCC Network’s response to COVID-19 Convalescent Plasma, Cell Therapy and Novel Vaccine Approaches

Panelists

Michael Matthay, MD, UC San Francisco: ARDS Program

Rachael Callcut, MD, MSPH, FACS, UC Davis: ARDS Program 

John Zaia, MD, City of Hope: Convalescent Plasma Program 

Daniela Bota, MD, PhD, UC Irvine: Natural Killer Cells as a Treatment Strategy 

Key questions for panelists: 

  • Describe your trial or clinical program?
  • What steps did you take to provide access to disproportionately impacted communities?
  • How is it part of the overall scientific response to COVID-19? 
  • How has the ASCC Network infrastructure accelerated this response? 

Brief Break

Roundtable 2: Moderator Ysabel Duron, The Latino Cancer Institute and Latinas Contra Cancer

View Recording: Roundtable 2

Community Engagement and Lessons Learned from the COVID Programs.  

Panelists

Marsha Treadwell, PhD, UC San Francisco: Community Engagement  

Sheila Young, MD, Charles R. Drew University of Medicine and Science: Convalescent Plasma Program in the community

David Lo, MD, PhD,  UC Riverside: Bringing a public health perspective to clinical interventions

Key questions for panelists: 

  • What were important lessons learned from the COVID programs? 
  • How can CIRM and the ASCC Network achieve equipoise among communities and engender trust in clinical research? 
  • How can CIRM and the ASCC Network address structural barriers (e.g. job constrains, geographic access) that limit opportunities to participate in clinical trials?

How stem cells are helping her win the fight of her life

We have all read about people who smoke a pack of cigarettes and drink a bottle of whiskey a day and somehow manage to live a long, healthy life. Then there are people like Sandra Dillon. She lived as healthy a life as you can imagine; she exercised a lot, ate a healthy diet and didn’t smoke. Yet at the age of 28 she was diagnosed with a rare and deadly form of blood cancer called myelofibrosis.

Sandra underwent the traditional forms of treatment but those proved ineffective and time seemed to be running out. Then she heard about a clinical trial for a new, experimental stem cell therapy, with Dr. Catriona Jamieson at the University of California San Diego.

Sandra says she wasn’t looking forward to it, but she was in a lot of pain, was getting much sicker and none of the treatments she tried was working.

“At the time I was actually quite afraid of seeing doctors or going to medical institutions. My experience had been rough, and I knew that I had to overcome my fear of going to hospitals and being treated. But it was a chance to have hope and to be on something that might work when there was nothing else available.”

Dr. Jamieson’s approach (CIRM helped support her early work in this area) had led to her identifying how abnormal gene activity was responsible for the progression of this form of blood cancer. With that knowledge she then identified a specific small molecule known to inhibit this mutant gene activity, and how it could halt the disease.

That’s what happened with Sandra. She says after years of pain and exhaustion, of fearing that she was running out of time, the treatment produced impressive results.

“It was pretty amazing. I had really low expectations from how sick I was and that this was experimental, and it was cancer and you expect it to be awful. And my experience was the opposite of what I’d expected. I started to feel incredible. The pain, after a few months, the side effects from my cancer started to come down.”

Today Sandra’s cancer is still in remission. She is back to her old, healthy, energetic self. She says she doesn’t consider herself a stem cell pioneer but is glad her participation in the trial might also benefit others.

“It’s helped me but the opportunity that it could also help other people is truly meaningful.”

The treatment she received was approved by the US Food and Drug Administration in 2019, the first approval for a therapy that had CIRM support.

I recently had the great pleasure of interviewing Sandra as part of our CIRM 2020 Grantee Meeting.

Repairing damaged muscles

Close-up of the arm of a 70-year-old male patient with a torn biceps muscle as a result of a bowling injury; Photo courtesy Science Photo Library

In the time of coronavirus an awful lot of people are not just working from home they’re also working out at home. That’s a good thing; exercise is a great way to boost the immune system, stay healthy and deal with stress. But for people used to more structured workouts at the gym it can come with a downside. Trying new routines at home that look easy on YouTube, but are harder in practice could potentially increase the risk of injury.

A new study from Japan looks at what happens when you damage a muscle. It won’t help it heal faster, but it will at least let you understand what is happening inside your body as you sit there with ice on your arm and ibuprofen in your hand.

The researchers found that when you damage a muscle, for example by trying to lift too much weight or doing too many repetitions of one exercise, the damaged muscle fibers leak substances that activate nearby “satellite” stem cells. These satellite cells then flock to the site of the injury and help repair the muscle.

The team, from Kumamoto University and Nagasaki University in Japan, named the leaking substances “Damaged myofiber-derived factors” (DMDFs) – personally I think “Substances Leaked by Injured Muscles (SLIM) would be a much cooler acronym, but that’s just me. Gaining a deeper understanding of how DMDFs work might help lead to therapies for older people who have fewer satellite muscle cells, and also for conditions like muscular dystrophy and age-related muscular fragility (sarcopenia), where the number and function of satellite cells decreases.

In an article in Science Daily, Professor Yusuke Ono, the leader of the study, says it’s possible that DMDFs play an even greater role in the body:

“In this study, we proposed a new muscle injury-regeneration model. However, the detailed molecular mechanism of how DMDFs activate satellite cells remains an unclear issue for future research. In addition to satellite cell activation, DMDF moonlighting functions are expected to be diverse. Recent studies have shown that skeletal muscle secretes various factors that affect other organs and tissues, such as the brain and fat, into the bloodstream, so it may be possible that DMDFs are involved in the linkage between injured muscle and other organs via blood circulation. We believe that further elucidation of the functions of DMDFs could clarify the pathologies of some muscle diseases and help in the development of new drugs.”

The study appears in the journal Stem Cell Reports.

Partners in health

From left to right: Heather Dahlenburg, Jan Nolta, Jeannine Logan White, Sheng Yang
From left to right: Heather Dahlenburg, staff research associate; Jan Nolta, director of the Stem Cell Program; Jeannine Logan White, advanced cell therapy project manager; Sheng Yang, graduate student, Bridges Program, Humboldt State University, October 18, 2019. (AJ Cheline/UC Davis)

At CIRM we are modest enough to know that we can’t do everything by ourselves. To succeed we need partners. And in UC Davis we have a terrific partner. The work they do in advancing stem cell research is exciting and really promising. But it’s not just the science that makes them so special. It’s also their compassion and commitment to caring for patients.

What follows is an excerpt from an article by Lisa Howard on the work they do at UC Davis. When you read it you’ll see why we are honored to be a part of this research.

Gene therapy research at UC Davis

UC Davis’ commitment to stem cell and gene therapy research dates back more than a decade.

In 2010, with major support from the California Institute for Regenerative Medicine (CIRM), UC Davis launched the UC Davis Institute for Regenerative Cures, which includes research facilities as well as a Good Manufacturing Practice (GMP) facility.

In 2016, led by Fred Meyers, a professor in the School of Medicine, UC Davis launched the Center for Precision Medicine and Data Sciences, bringing together innovations such as genomics and biomedical data sciences to create individualized treatments for patients.

Last year, the university launched the Gene Therapy Center, part of the IMPACT Center program.

Led by Jan Nolta, a professor of cell biology and human anatomy and the director of the UC Davis Institute for Regenerative Cures, the new center leverages UC Davis’ network of expert researchers, facilities and equipment to establish a center of excellence aimed at developing lifelong cures for diseases.

Nolta began her career at the University of Southern California working with Donald B. Kohn on a cure for bubble baby disease, a condition in which babies are born without an immune system. The blood stem cell gene therapy has cured more than 50 babies to date.

Work at the UC Davis Gene Therapy Center targets disorders that potentially can be treated through gene replacement, editing or augmentation.

“The sectors that make up the core of our center stretch out across campus,” said Nolta. “We work with the MIND Institute a lot. We work with the bioengineering and genetics departments, and with the Cancer Center and the Center for Precision Medicine and Data Sciences.”

A recent UC Davis stem cell study shows a potential breakthrough for healing diabetic foot ulcers with a bioengineered scaffold made up of human mesenchymal stem cells (MSCs). Another recent study revealed that blocking an enzyme linked with inflammation enables stem cells to repair damaged heart tissue. A cell gene therapy study demonstrated restored enzyme activity in Tay-Sachs disease affected cells in humanized mouse models.

Several cell and gene therapies have progressed to the point that ongoing clinical trials are being conducted at UC Davis for diseases, including sickle-cell anemia, retinopathy, muscle injury, dysphasia, advanced cancer, and Duchenne muscular dystrophy, among others.

“Some promising and exciting research right now at the Gene Therapy Center comes from work with hematopoietic stem cells and with viral vector delivery,” said Nolta.

Hematopoietic stem cells give rise to other blood cells. A multi-institutional Phase I clinical trial using hematopoietic stem cells to treat HIV-lymphoma patients is currently underway at UC Davis.

.Joseph Anderson

Joseph Anderson

“We are genetically engineering a patient’s own blood stem cells with genes that block HIV infection,” said Joseph Anderson, an associate professor in the UC Davis Department of Internal Medicine. The clinical trial is a collaboration with Mehrdad Abedi, the lead principal investigator.

“When the patients receive the modified stem cells, any new immune system cell, like T-cell or macrophage, that is derived from one of these stem cells, will contain the HIV-resistant genes and block further infection,” said Anderson.

He explained that an added benefit with the unique therapy is that it contains an additional gene that “tags” the stem cells. “We are able to purify the HIV-resistant cells prior to transplantation, thus enriching for a more protective cell population.

Kyle David Fink

Kyle David Fink

Kyle David Fink, an assistant professor of neurology at UC Davis, is affiliated with the Stem Cell Program and Institute for Regenerative Cures. His lab is focused on leveraging institutional expertise to bring curative therapies to rare, genetically linked neurological disorders.

“We are developing novel therapeutics targeted to the underlying genetic condition for diseases such as CDKL5 deficiency disorder, Angelman, Jordan and Rett syndromes, and Juvenile Huntington’s disease,” said Fink.

The lab is developing therapies to target the underlying genetic condition using DNA-binding domains to modify gene expression in therapeutically relevant ways. They are also creating novel delivery platforms to allow these therapeutics to reach their intended target: the brain.

“The hope is that these highly innovative methods will speed up the progress of bringing therapies to these rare neurodegenerative disease communities,” said Fink.Jasmine Carter, a graduate research assistant at the UC Davis Stem Cell Program.

Jasmine Carter, a graduate research assistant at the UC Davis Stem Cell Program, October 18, 2019. (AJ Cheline/UC Davis)

Developing potential lifetime cures

Among Nolta’s concerns is how expensive gene therapy treatments can be.

“Some of the therapies cost half a million dollars and that’s simply not available to everyone. If you are someone with no insurance or someone on Medicare, which reimburses about 65 percent, it’s harder for you to get these life-saving therapies,” said Nolta.

To help address that for cancer patients at UC Davis, Nolta has set up a team known as the “CAR T Team.”

Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy in which a patient’s own immune cells are reprogrammed to attack a specific protein found in cancer cells.

“We can develop our own homegrown CAR T-cells,” said Nolta. “We can use our own good manufacturing facility to genetically engineer treatments specifically for our UC Davis patients.”

Although safely developing stem cell treatments can be painfully slow for patients and their families hoping for cures, Nolta sees progress every day. She envisions a time when gene therapy treatments are no longer considered experimental and doctors will simply be able to prescribe them to their patients.

“And the beauty of the therapy is that it can work for the lifetime of a patient,” said Nolta.

Exploring tough questions, looking for answers

COVID-19 and social and racial injustice are two of the biggest challenges facing the US right now. This Thursday, October 8th, we are holding a conversation that explores finding answers to both.

The CIRM Alpha Stem Cell Clinic Network Symposium is going to feature presentations about advances in stem cell and regenerative research, highlighting treatments that are already in the clinic and being offered to patients.

But we’re also going to dive a little deeper into the work we support, and use it to discuss two of the most pressing issues of the day.

One of the topics being featured is research into COVID-19. To date CIRM has funded 17 different projects, including three clinical trials. We’ll talk about how these are trying to find ways to help people infected with the virus, seeing if stem cells can help restore function to organs and tissues damaged by the virus, and if we can use stem cells to help develop safe and effective vaccines.

Immediately after that we are going to use COVID-19 as a way of exploring how the people most at risk of being infected and suffering serious consequences, are also the ones most likely to be left out of the research and have most trouble accessing treatments and vaccines.

Study after study highlights how racial and ethnic minorities are underrepresented in clinical trials and disproportionately affected by debilitating diseases. We have a responsibility to change that, to ensure that the underserved are given the same opportunity to take part in clinical trials as other communities.

How do we do that, how do we change a system that has resisted change for so long, how do we overcome the mistrust that has built up in underserved communities following decades of abuse? We’ll be talking about with experts who are on the front lines of this movement.

It promises to be a lively meeting. We’d love to see you there. It’s virtual – of course – it’s open to everyone, and it’s free.

Here’s where you can register and find out more about the Symposium