Disease Areas

Join the movement to fight rare diseases

/ Katie Sharify / 2 Comments

Tomorrow, February 28th, is Rare Disease Day. It’s a day to remind ourselves of the millions of people, and their families, struggling with these diseases. These conditions are also called orphan diseases because, in many cases, drug companies were not interested in adopting them to develop treatments.

Here at the California Institute for Regenerative Medicine (CIRM), we understand the importance of funding research that impacts not just the most common diseases. In fact, 50% of all the projects we fund target a rare disease or condition such as: Retinitis pigmentosa, Sickle cell disease, Huntington’s disease, and Duchenne Muscular Dystrophy.

Over the years, CIRM has invested millions of dollars in helping children born with severe combined immunodeficiency (SCID), including $12 million to test a newly designed therapy in a clinical trial at UC San Francisco.

Children born with SCID have no functioning immune system so even a simple infection can prove life-threatening or fatal. We recently shared an update from one of the young patients in the trial.

Additionally, last December, the CIRM governing Board awarded $4,048,253 to Dr. Joseph Anderson and his team at UC Davis to develop a blood stem cell gene therapy for the treatment of Tay-Sachs disease.

Tay-Sachs disease is a rare genetic disorder where a deficiency in the Hex A gene results in excessive accumulation of certain fats in the brain and nerve cells and causes progressive dysfunction.  

There are several forms of Tay-Sachs disease, including an infant, juvenile, and adult forms. Over a hundred mutations in the disease-causing Hex A gene have been identified that result in enzyme disfunction. There are currently no effective therapies or cures for Tay-Sachs. 

The irony of rare diseases is that a lot of people have them. The total number of Americans living with a rare disease is estimated at between 25-30 million. Two-thirds of these patients are children.

Right now, individual disease programs tend to try individual approaches to developing a treatment, which is time consuming and expensive. That’s why this past summer, CIRM signed a Memorandum of Understanding (MOU) with the Foundation for the National Institutes of Health (FNIH) to join the Bespoke Gene Therapy Consortium (BGTC).

BGTC is a public-private partnership, managed by FNIH, that brings together the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA), and multiple public and private sector organizations to streamline the development and delivery of gene therapies for rare diseases.

“At CIRM we have funded several projects using gene therapy to help treat, and even cure, people with rare diseases such as severe combined immunodeficiency,” says Dr. Maria T. Millan, the President and CEO of CIRM. “But even an agency with our resources can only do so much. This agreement with the Bespoke Gene Therapy Consortium will enable us to be part of a bigger partnership, one that can advance the field, overcome obstacles and lead to breakthroughs for many rare diseases.”

CIRM is proud to fund and spread awareness of rare diseases and invites you to watch this video about how they affect families around the world.

Investing in stem cell and gene therapy treatments for HIV

/ Esteban Cortez / 1 Comment

A recent article in Nature shared the news about a 53-year-old man in Germany who was declared free of HIV after receiving virus-resistant cells. 

The man—referred to as the “Düsseldorf patient”—was diagnosed with acute myeloid leukemia and underwent a stem cell transplant in 2013 that replaced his bone marrow cells with HIV-resistant stem cells from a donor.  

In the five years following the procedure, virologist Björn-Erik Jensen and his team at Düsseldorf University Hospital in Germany continued to monitor the patient. They continued to find immune cells that reacted to HIV in his body, which suggested that his body was not clear of the virus. 

In 2018, the patient stopped taking antiretroviral therapy (ART), a treatment for HIV that reduces a person’s viral load to an undetectable level. His body has remained HIV-free since then, indicating that the stem cell transplant worked.  

Similar stem cell treatments have been used to treat others living with HIV, including a patient in 2007 and another patient in 2019. 

The article in Nature states that the procedure is unlikely to be used widely in its current form due to the associated risks, including the chance that an individual will reject a donor’s marrow.  

Scientists continue to test stem cells as a treatment for HIV, including methods in which cells are taken from a person’s own body and genetically modified, eliminating the need for donor cells. 

CIRM’s Commitment to Investing in Treatments for HIV

The news of the Düsseldorf patient shows the importance of continued stem cell and gene therapy research to find treatments for HIV.  

At the California Institute for Regenerative Medicine (CIRM), we have invested more than $85 million in the search for stem cell and gene therapy treatments for HIV/AIDS, ranging from basic Discovery research to clinical trials.  

Recent CIRM investments include a study at UC Davis health, in which researchers take a patient’s own white blood cells, called T-cells, and modify them so that they can identify and target HIV cells to control the virus without medication. 

CIRM also funded a clinical trial at UCSF to develop a functional cure for HIV/AIDS. In the trial, the team takes a patient’s blood and extracts 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. 

Last year, researchers in the UCSF trial shared that they had dosed the first patient in the trial testing their anti-HIV duoCAR-T cell therapy. You can read the announcement here.  

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. 

To learn more about CIRM’s commitment and investments in finding treatments for HIV, visit our website. 

CIRM board member Ysabel Duron appointed to National Cancer Advisory Board by President Biden

/ Esteban Cortez / Leave a comment

Ysabel Duron is an award-winning journalist, patient advocate, cancer survivor and board member of the California Institute for Regenerative Medicine (CIRM). 

Her list of achievements continues to grow, as President Biden has appointed Duron to National Cancer Advisory Board (NCAB), which plays an important role in setting the course for the national cancer research program. 

The National Cancer Advisory Board will complement the Cancer Moonshot, which President Biden reignited a year ago to invest in research and development that will help advance breakthroughs to prevent, detect and treat diseases like cancer. 

“As a Latina, and a long-time patient and community advocate, it humbles me to join this roster of stellar new appointees,” Duron said. “I look forward to the challenge of amplifying the voices of racial and ethnic communities and other vulnerable populations.” 

Duron came into the cancer space after her own bout with Hodgkins Lymphoma in 1999. She covered her own cancer battle using her reporting skills to raise awareness about the disease.  

Over time, she turned a spotlight on the many disparities—lack of access, income inequality, language barriers, among other social determinants on health—that has exacerbated the disproportionate burden of cancer in Latino communities. 

In 2017, Ms. Duron founded The Latino Cancer Institute (TLCI), a nationwide network dedicated to developing and sharing best practice programs to enhance the work of Latino community service agencies, to provide collaboration with the global cancer research community, and drive policy to solve the issues and burden of Latinx/Hispanic cancer. 

In addition to her new appointment to the NCAB and role as Board member at CIRM, Duron also serves on the Institutional Review Board for the NIH/All of Us Research program. She also recently joined the newly launched American Cancer Society National Breast Cancer Roundtable. 

Read the official White House press release here.

California agency invests $4 million in stem cell treatment for Parkinson’s Disease

/ Esteban Cortez / 2 Comments

The California Institute for Regenerative Medicine (CIRM) is investing $4 million in a late-stage preclinical project by Ryne Bio aiming to improve treatment for Idiopathic Parkinson’s disease (PD).

PD is characterized by a loss of dopamine producing neurons that result in motor symptoms, such as dyskinesias (involuntary, erratic, writhing movements of the face, arms, legs or trunk) and non-motor effects such as dementia, depression and sleep disorders.

PD is the second-most common neurodegenerative disease after Alzheimer’s disease affecting approximately 1 million people in the U.S. In California, it is estimated that 116,900 people live with PD, representing the highest number of people with the disease in the country.

At its early stages, PD can be treated with medication such as Levodopa to treat symptoms but these become less effective as the disease progresses.

The proposed stem cell therapy in this project offers the potential to restore dopamine neurons, which play a role in many important body functions, including movement and memory.

Investigators at Ryne Bio are aiming to deliver dopamine producing cells to replace the lost neurons to the brain of Parkinson’s disease patients to restore/improve motor function.

The current grant is being funded to conduct Investigational New Drug (IND) enabling, nonclinical safety studies per the US Food and Drug Administration (FDA) Guidance. The IND is the authorization needed to begin a clinical trial in Parkinson’s patients.

CIRM has a vested interest in seeing this therapy succeed. To date, CIRM has invested more than $59 million in helping research for Parkinson’s disease progress from a basic or Discovery level through clinical trials.

Investing in CAR T-cell therapy to treat cancer

/ Katie Sharify / 1 Comment
Photo credit: UC Regents 

The California Institute for Regenerative Medicine (CIRM) is investing $4 million to support Dr. William Murphy and UC Davis researchers to develop and test a chimeric antigen receptor (CAR) T-cell therapy to treat various B-cell malignancies, ranging from lymphomas to leukemias. 

In this Q&A—courtesy of UC Davis Health—Dr. Murphy discusses the importance of T-cell therapy and its implications for developing cancer treatments. His work is a collaboration between CIRM, the nonprofit organization Caring Cross, and UC Davis Health. 

What are B-cell malignancies? 

B-cells are a type of white blood cells that make antibodies. They are key to the body’s immune system. When healthy B-cells change into fast-growing cancer cells that don’t die, they cause B-cell malignancies. 

This can affect people at different ages. They may show up in children as B-cell acute lymphoblastic leukemia (B-ALL), an aggressive blood and bone marrow cancer. In adults, they make up about 85% of non-Hodgkin lymphoma (NHL), a cancer that starts in B lymphocytes. In the elderly, B-cell malignancies may come as multiple myeloma, a cancer of the plasma cells. 

There are different lines of treatments for B-cell lymphoma and leukemia, including immunotherapy using chimeric antigen receptor (CAR) T cells. These cells have revolutionized cancer treatment since they have been shown to work, and cure, when nothing else can. 

What is chimeric antigen receptor (CAR) T-cell therapy? 

Chimeric antigen receptor (CAR) T-cell therapy uses the body’s own defenses to fight disease. It is a new and exciting form of immunotherapy that works by modifying the receptors of immune cells (T cells) involving antibodies to target specific cancers, such as leukemias and lymphomas. 

CAR T cells are being used to treat some blood cancers with long-term success. The U.S. Food and Drug Administration (FDA) first approved CAR T-cell therapy in 2017. Their use is growing rapidly and being applied to other tumor types. Yet, this therapy is extremely expensive, even with insurance. It’s also a very intensive procedure and it takes time to generate the CAR T cells from the patient. 

While it could be considered a game changer, one of the issues with this therapy is the case relapse rate. The big holy grail in cancer therapy is how to prevent tumors from evading or escaping the immune attack. Around 60% of patients who get CAR therapy see their cancer return. If we can get the relapse rate down to negligible, that would be a tremendous advance. 

How do you intend to use CAR products to reduce cancer relapse? 

In CAR therapy, we take the immune T cells from a patient and use gene therapy to give a new receptor to signal and direct the T cell. The receptor usually has an antibody that recognizes a particular tumor antigen. Current FDA-approved CAR T therapies only target one tumor antigen. 

CARs have had tremendous success. However, there is significant patient relapse because the tumor adapts and may lose that one antigen that we are targeting, allowing it to escape the treatment. Our strategy is to target multiple antigens to reduce the potential for relapse since the tumor cannot adapt that quickly. 

We are also proposing a novel vector that will carry a CAR product, known as DuoCAR, that targets three antigens at the same time. As long as the tumor has one of the three antigens, then there’s little chance for the tumor to escape all three antibodies. This is similar to when you think about HIV treatment with the triple-drug therapy, where one alone is not sufficient. 

The hope is that the 60 to 70% of the population who would have relapsed if they had the original CAR T cell treatment, would have a home run with our kind of treatment or product. 

So, is this treatment for cancer patients who have relapsed? 

We see this product as a new frontline therapy and not just for patients who relapse. What the patient has to go through in order for CAR T therapy to work is very strenuous. So, yes, if there are relapsed patients, they can be given DuoCAR, but we’re also hoping this will become the new standard of care, replacing the other CARs in the future for everyone. 

To read the full Q&A, click here. 

Update on SCID patient enrolled in CIRM-funded gene therapy trial

/ Katie Sharify / 2 Comments
Photo credit: UCSF

Hataalii Tiisyatonii Begay (HT) is paving the road for newborns with SCID. When HT was born in 2018 in a remote part of the Navajo nation, he was quickly diagnosed with a rare and -usually fatal- condition. Today, thanks to a therapy developed at UCSF and funded by CIRM, he’s a healthy four-year-old boy running around in cowboy boots.

The California Institute for Regenerative Medicine (CIRM) has invested $12 million to test this therapy in a clinical trial at UC San Francisco.

The disorder is Artemis-SCID, a form of severe combined immunodeficiency disease. Children born with this condition have no functioning immune system so even a simple infection can prove life-threatening or fatal.

Currently, the only approved treatment for Artemis-SCID is a bone-marrow transplant, but many children are unable to find a healthy matched donor for that procedure. Even when they do find a donor, they often need regular injections of antibodies to boost their immune system.

Dr. Morton Cowen and Dr. Jennifer Puck. Photo credit: UCSF

In this clinical trial, UCSF doctors Morton Cowan and Jennifer Puck are using the patient’s own blood stem cells, taken from their bone marrow. In the lab, the cells are modified to correct the genetic mutation that causes Artemis-SCID and then re-infused back into the patients. The goal is that over the course of several months these cells will create a new blood supply, one that is free of Artemis-SCID, and that will in turn help repair the child’s immune system.

In April 2022, HT finally moved back home to Arizona. Nowadays, HT is off his medication and living the life of a normal and happy young child. On the Arizona ranch, there are horses to pet, cattle and sheep to tend, and streams to cool his hands in.

Watch the video below to find out more about HT’s journey and the team at UCSF behind the pioneering trial.

Video courtesy of UCSF

Funding development of a vaccine for acute myelogenous leukemia (AML)

/ Esteban Cortez / 2 Comments
Dr. Karin Gaensler. Photo credit: Steve Babuljak/UCSF

Adult acute myelogenous leukemia—also known as acute myeloid leukemia (AML)—is a blood cancer in which the bone marrow makes a large number of abnormal blood cells. 

About 20,000 new cases of AML are diagnosed each year in the US with a 5-year survival rate of around 29%. In 2022, there were nearly 12,000 deaths from AML. Many AML patients—a majority of which are over 60 years old—relapse after treatment. Blood stem cell transplant can be curative, but many older patients do not qualify, showing that there is a significant unmet medical need in treating AML. 

That’s why the California Institute for Regenerative Medicine (CIRM) awarded $6,000,000 to Dr. Karin Gaensler at the University of California, San Francisco (UCSF) to support development of a safe and effective vaccine for the blood cancer AML to improve relapse-free survival. 

To develop the cancer vaccine, Dr. Gaensler and her team will engineer the patient’s blood stem cells to maximize stimulation of leukemia-specific killing activity and reintroduce engineered cells back to the patient to target and kill residual leukemia stem cells.  

This approach holds the potential for long-term effectiveness as it targets both AML blasts and leukemic stem cells that are often the source of relapse.  

This award is a continuation of a previous CIRM grant that will support the manufacture of the vaccine and the completion of late-stage testing and preparation needed to apply to the US Food and Drug Administration (FDA) for permission to begin a clinical trial. 

CIRM funds clinical trial to make cancer therapy safer, less toxic

/ Esteban Cortez / 1 Comment

Blood stem cell transplantation following high dose chemotherapy is standard of care and potentially curative for aggressive forms of lymphoma. However, this treatment regimen is limited by severe toxicity and life-threatening complications due to delayed recovery of the blood system and vascular related damage of multiple organs.

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) funded a Phase 3 clinical trial to support development of a safer, more tolerable alternative.

This brings the number of clinical trials funded by CIRM to 86.

The Board awarded $15,000,000 to Dr. Paul Finnegan and Angiocrine Bioscience to test AB-205, human endothelial cells engineered to express a pro-survival factor.

Prior data suggest that, in the setting of chemotherapy and stem cell transplantation, AB-205 cell therapy can accelerate the recovery of the blood system and protects from toxicity by enhancing the recovery from vascular damage. AB-205 is being studied in a Phase 3 trial in adults with lymphoma undergoing high-dose chemotherapy and autologous blood stem cell transplant.

“If successful, this approach can overcome hurdles to the success of chemotherapy and blood stem cell transplantation for the treatment of advanced blood cancer,” says Dr. Maria T. Millan, President and CEO of CIRM. “This Phase 3 trial is the culmination of preclinical research and the initial clinical trial previously funded by CIRM.”

Lymphoma is the most common blood cancer and one of the most common cancers in the United States, accounting for about 4% of all cancers according to the American Cancer Society and the 6th most commonly diagnosed cancer among men and women in California.  It is estimated that there will be 89,010 new cases of lymphoma and 21,170 lymphoma related deaths in the US in 2022 alone.  In California, it is estimated that there will be over 9,250 new cases of lymphoma with over 2,100 deaths.

“Angiocrine Bioscience is honored to be awarded this grant from CIRM to support our AB-205 Phase 3 trial,” commented Angiocrine CEO Dr. Paul Finnegan. “CIRM has been an instrumental partner in our development of AB-205, a novel therapeutic that acts on the patients’ endogenous stem cell niches. The grant award will considerably aid in our effort to bring forth a solution to the unmet need of transplant-related complications.”

Update on spinal cord injury patient enrolled in CIRM-funded stem cell clinical trial

/ Katie Sharify / Leave a comment
Jake Javier and his parents at Duke University

A spinal cord injury (SCI) is devastating, changing a person’s life in an instant. Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury. Most of these are caused by trauma to the spinal column, thereby affecting the spinal cord’s ability to send and receive messages from the brain to the body’s systems that control sensory, motor and autonomic function below the level of injury.

Currently, there is nothing that completely reverses SCI damage and most treatment is aimed at rehabilitation and empowering patients to lead as normal a life as possible under the circumstances. Improved treatment options are necessary both to improve patients’ overall quality of life, and to reduce associated healthcare costs.

In 2010, the Geron trial became not only the first clinical trial to be funded by the California Institute for Regenerative Medicine (CIRM), but the first clinical trial in the world using embryonic stem cells.

By 2014, Asterias Biotherapeutics (now Lineage Cell Therapeutics Inc.), acquired the cell therapy assets of Geron and launched its Phase 1/2a clinical trial with the goal of determining the safety of the therapy and the optimal dose of cells to transplant into patients.

In 2016, Jake Javier became the fifth patient to participate in the revived Asterias trial. Regular readers of our blog will remember that Jake is the young man who broke his neck the day before he graduated high school, leaving him paralyzed from the upper chest down.

After enrolling in the CIRM-funded Asterias clinical trial, and receiving a transplant of ten million stem cells, Jake regained enough use of his arms and hands to be able to go to Cal Poly and start his life over.

This video highlights the struggles and challenges he faced in his first year, and his extraordinary spirit in overcoming them.

Video courtesy of Matt Yoon and his team at Cal Poly

Today, Jake is set to graduate from Duke University with his master’s degree in Biomedical Engineering, with plans to help those impacted by neurological injuries or disease.

Watch the video below to learn more about Jake’s personal perspective on his clinical trial participation, the OPC1 clinical study, his future plans and his message to the SCI community.

Video courtesy of Lineage Cell Therapeutics Inc.

Lab-made retinas offer a new approach to battling vision loss

/ Kevin McCormack / 3 Comments

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. Now, new research using 3D organoid models of the eye has uncovered clues as to what happens in AMD, and how to stop it. 

In AMD, a person loses their central vision because the light sensitive cells in the macula, a part of the retina, are damaged or destroyed. This impacts a person’s ability to see fine details, recognize faces or read small print, and means they can no longer drive. 

AMD causes blurry and distorted vision 

No one is quite sure what causes AMD, but in a study in the journal Nature Communications, German researchers used miniature human retina organoids to get some clues.  

Building a better model for research

Organoids are 3D models made from human cells that are grown in the lab. Because they have some of the characteristics of a human organ—in this case the retina—they help researchers better understand what is happening in the AMD-affected eye. 

In this study they found that photoreceptors, the light sensitive cells at the back of the retina, were missing but there was no sign of dead cells in the organoid. This led them to suspect that something called cell extrusion was at play.  

Cell extrusion is where a cell exports or sends large particles outside the cell. In this case it appeared that something was causing these photoreceptors to be extruded, leading to the impaired visual ability.  

In a news release Mark Karl, one of the authors of the study, said, “This was the starting point for our research project: we observed that photoreceptors are lost, but we could not detect any cell death in the retina. Half of all photoreceptors disappeared from the retinal organoid within ten days, but obviously they did not die in the retina. That made us curious.” 

Using snakes to fight AMD 

Further research identified two proteins that appeared to play a key role in the process, triggering the degeneration of the retinal organoid. They also tested a potential therapy to see if they could stop the process and save the photoreceptors. The therapy they tried, a snake venom, not only stopped the photoreceptors from being ejected, but it also prevented further damage to the retinal cells. 

Karl says this is the starting point for the next step in the research. “This gives hope for the development of future preventive and therapeutic treatments for complex neurodegenerative diseases such as AMD.” 

CIRM’s fight against blindness 

The California Institute for Regenerative Medicine (CIRM) has funded six clinical trials targeting vision loss, including one for AMD. We recently interviewed Dr. Dennis Clegg, one of the team trying to develop a treatment for AMD and he talked about the encouraging results they have seen so far. You can hear that interview on our podcast “Talking ‘Bout (re)Generation.”