UC Irvine Receives Funding for Clinical Trial of Neural Stem Cell Therapy for Huntington's Disease

UC Irvine Receives Funding for Clinical Trial of Neural Stem Cell Therapy for Huntington's Disease

Leslie M. Thompson, Donald Bren Professor of Psychiatry and Human Behavior and Neurobiology and Behavior at the University of California, Irvine, received $11,999,933 California Institute for Regenerative Medicine grant for an unprecedented clinical trial of a novel neural stem cell therapy for Huntington's disease.

This award supports a first-in-human safety and tolerability study of an embryonic stem cell-derived neural stem cell product for the treatment of Huntington's disease, a milestone for patients currently lacking therapies that could alter the course of this devastating disease.

The study will focus on the safety of the cell product, which it is hoped can protect brain cells, repair damaged brain circuits and slow or prevent disease progression in humans. This will be the first test of embryonic stem cell-derived cells in people with Huntington's disease; Previous experiments have used cells from fetal cells or tissue. The clinical trial is scheduled to begin in mid-2026. This novel cell therapy has been extensively tested in preclinical safety and efficacy studies and promises to advance the treatment of Huntington's disease.

Huntington's disease is a genetic disease which gradually destroys brain cells, usually starting between the ages of 35 and 50 and getting worse over 10 to 20 years. Symptoms include involuntary movements, difficulty thinking and planning daily tasks, and mood changes such as depression.

The therapy being tested, called hNSC-01, uses neural stem cells that can protect existing brain cells from dying, replace lost cells, rebuild compromised brain circuits, release helpful proteins like BDNF that are low in HD patients, and reduce harmful protein buildups that damage brain cells. These results have all been demonstrated in animal studies, where the cells also improved movement, restored brain function and were shown to be safe over long periods of time.

The clinical trial at UC Irvine will take part 21 people with early-stage Huntington's disease, including 12 participants in a Phase 1B dose escalation group and nine in a Phase 2A expansion group. The cells are surgically inserted into the brain and subjects are closely monitored for safety and early signs of possible benefit.

Huntington's disease places an enormous burden on patients, families and caregivers, often lasting for decades. In California alone, hospital costs for HD patients can range from $3 million to $25 million per year. If successful, this therapy could allow people with Huntington's disease to live independently longer, significantly reducing long-term care costs and thus reducing the burden on families.

This study is an exciting step for regenerative medicine and its potential to change the course of Huntington's disease. It provides additional hope to patients and families who currently have very few options.”

Leslie M. Thompson, Principal Investigator, Professor of Biological Chemistry, University of California, Irvine

She added: "The award is the culmination of the tremendous efforts of a team of researchers, including Dr. Jack Reidling and Yuna Muyshondt from UC Irvine and the UC Davis GMP facility, which produced the cell product."

Thompson has been working on Huntington's disease for more than three decades and has received $17.6 million in CIRM funding to advance both basic research and translational pathways. In 2019, she received $6 million to develop stem cell-based therapies for Huntington's disease. With this initiative, an investigational new drug application has now been approved by the FDA, paving the way for the current award that funds the UC Irvine Alpha Clinic's early-stage human clinical trial.

In October of this year, Thompson received $2 million in CIRM funding to explore one of medicine's most perplexing mysteries: why Huntington's disease destroys some brain cells while sparing others. Her lab integrates patient-derived stem cells, transcriptomics, proteomics and bioinformatics to study disease mechanisms while pioneering new avenues to understand why certain brain cells are more susceptible to Huntington's disease than others. Additionally, Thompson is co-director of the Sue & Bill Gross Stem Cell Research Center at UC Irvine.

This award is part of CIRM's clinical trial-stage projects, which aim to accelerate promising stem cell therapies from late preclinical development stages through clinical trials to address unmet medical needs.

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