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 as well as neurobiology and behavior at the University of California, Irvine, has received an $11,999,933 grant from the California Institute for Regenerative Medicine for an unprecedented clinical trial of a novel neural stem cell therapy for Huntington's disease.

This award will support a first-in-humans safety and tolerability study of an embryonic stem cell-derived neural stem cell product for Huntington's disease, a milestone for patients who currently have no available therapies that alter the course of this devastating disorder.

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 initial test of embryonic stem cell-derived cells in people with Huntington's disease; previous trials used cells from fetal cells or tissue. The clinical trial is expected to begin in mid-2026. This novel cell therapy has been tested extensively in preclinical safety and efficacy studies and shows promise to advance treatment for HD.

Huntington's disease is a genetic disorder that gradually destroys brain cells, usually starting between the ages of 35 and 50 and worsening 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, utilizes neural stem cells that can protect existing brain cells from dying, replace lost cells, rebuild impaired brain circuits, release helpful proteins such as BDNF that are low in HD patients, and reduce harmful protein accumulations that damage brain cells. These outcomes have all been demonstrated in animal studies, in which the cells also improved movement, restored brain function and were shown to be safe over long periods.

The clinical trial at UC Irvine will enroll 21 people with early-stage Huntington's disease, with 12 participants in a Phase 1B dose-escalation group and nine in a Phase 2A expansion group. The cells will be surgically delivered into the brain, and subjects will be closely monitored for safety as well as preliminary signs of potential benefit.

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

"This trial is an exciting step for regenerative medicine and its potential to change the course of Huntington's disease," said principal investigator Thompson, who's also a professor of biological chemistry. "It provides additional hope to patients and families who currently have very few options."

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

Thompson has studied Huntington's for more than three decades and has received $17.6 million in CIRM funding to advance both fundamental science and translational avenues. In 2019, she was awarded $6 million to develop stem cell-based therapies for Huntington's, an effort that has since cleared an investigational new drug application with the FDA, paving the way for the current award that funds the early-phase clinical trial in humans through the UC Irvine Alpha Clinic.

In October of this year, Thompson got $2 million in CIRM funding to probe one of medicine's most baffling mysteries: why Huntington's disease devastates some brain cells while sparing others. Her laboratory integrates patient-derived stem cells, transcriptomics, proteomics and bioinformatics to investigate disease mechanisms, while also pursuing new paths to understanding why certain brain cells are more vulnerable than others to Huntington's disease. In addition, Thompson co-directs UC Irvine's Sue & Bill Gross Stem Cell Research Center.

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