First Patient Receives Neural Stem Cell Therapy in Pioneering Huntington's Disease Trial at UCI Health
Key Insights
The first participant has been dosed in the REGEN4HD Phase 1b/2a trial testing hNSC-01 (search), an embryonic stem cell-derived neural stem cell therapy for Huntington's disease (search).
The trial, led by Professor Leslie Thompson at UC Irvine and funded by a $12 million CIRM grant, will enroll 21 participants with early-stage HD in a dose-escalation design.
The primary goal is to assess safety and tolerability, with exploratory measures including motor scores, brain imaging, and biomarkers such as NfL and PENK.
The first participant has been dosed in a first-in-human clinical trial testing a neural stem cell therapy for Huntington's disease (search) (HD), marking a significant milestone for regenerative medicine approaches to this fatal neurodegenerative disorder. The REGEN4HD trial, conducted at UCI Health (search) under the University of California, Irvine, is evaluating hNSC-01 (search), a pluripotent neural stem cell therapy derived from embryonic stem cells and manufactured through the UC Davis GMP facility.
The first patient received the intervention in May 2026 at UCI Health (search) – Irvine, with UCI Health neurosurgeon Dr. Jefferson W. Chen delivering the cells, assisted by a neurosurgery fellow. "The first patient intervention went very well. To date, they haven't reported any serious adverse events," said Dr. Ravi Rajmohan, UCI Health neurologist and the clinical trial's principal investigator. A second patient is scheduled to receive the intervention in July.
"This clinical trial highlights the important role that an interdisciplinary academic and clinical team, together with the HD families, plays in advancing medicine," said Professor Leslie M. Thompson, Ph.D., Donald Bren Professor of psychiatry and human behavior as well as neurobiology and behavior at UC Irvine, who serves as the clinical trial sponsor. "We are grateful to our patients and their incredible families for their bravery to provide hope for others with very few options."
The Therapy: hNSC-01
hNSC-01 (search) consists of neural stem cells — immature cells capable of developing into the specialized cell types that constitute the brain and nervous system. In preclinical animal studies, the therapy has demonstrated the ability to protect existing brain cells, replace lost cells, rebuild impaired brain circuits, release helpful proteins such as brain-derived neurotrophic factor (BDNF), and reduce harmful protein accumulations that damage brain cells. The stem cells were also shown to be safe over long periods in mice.
The cells are implanted directly into the striatum, a deep brain region responsible for motor control, decision-making, and motivation that is among the earliest areas impacted in people carrying the HD gene change. The implantation is performed during a roughly six-hour surgical procedure under general anesthesia, with the patient lying face down in an MRI scanner. A specialized neurological mapping and targeting stereotactic system is used for precise navigation and delivery.
Trial Design and Endpoints
REGEN4HD is a Phase 1b/2a study that plans to enroll 21 participants between the ages of 18 and 65 with genetically confirmed, early-stage Huntington's disease (search). All participants will receive the treatment; there is no placebo group at this stage. Twelve participants will be enrolled into the Phase 1b dose-escalation group and nine in a Phase 2a expansion group.
The Phase 1b portion employs a stepwise dose-escalation across four cohorts: Cohort A receives a low dose in one side of the brain; Cohort B receives a low dose in both sides; Cohort C receives a medium dose in both sides; and Cohort D receives a high dose in both sides. This approach allows researchers to identify potential safety concerns before advancing to higher doses. The Phase 2a portion will then test the highest dose that appears safe and explore early signals of efficacy.
The primary focus of the trial is safety and tolerability. Investigators will closely monitor participants for possible side effects related to both the implanted cells and the surgical procedure, including immune reactions, altered blood work, neurological changes, and physical falls. Safety assessments will be intensive in the first several weeks after surgery, with longer-term follow-up extending to at least one year.
Although the study is not designed to prove effectiveness, researchers will collect a range of exploratory measurements to look for early hints of biological activity. These include the Unified Huntington's Disease (search) Rating Scale Total Motor Score (TMS), Total Functional Capacity (TFC), the Mini-Mental State Examination and Stroop Word Reading test, detailed brain imaging via MRI and PET scans, and biomarker measurements in blood and cerebrospinal fluid. Key biomarkers include neurofilament light chain (search) (NfL), a marker of brain cell injury, and proenkephalin (search) (PENK), which is thought to more specifically reflect the health of striatal neurons particularly vulnerable in HD.
Funding and Context
The clinical trial is made possible by a $12 million grant from the California Institute for Regenerative Medicine (search) (CIRM) and is coordinated through the UC Irvine Alpha Clinic, one of nine CIRM clinical research centers in California and the clinical arm of the UC Irvine Sue & Bill Gross Stem Cell Research Center.
Huntington's disease (search) is a fatal, progressive genetic disorder that gradually destroys brain cells, typically beginning between ages 35 and 50 and worsening over 10 to 20 years. Symptoms include involuntary movements, difficulty thinking and planning, and mood changes such as depression. In California alone, healthcare costs for Huntington's patients can range from $3 million to $25 million annually.
Cautious Outlook
Cell transplantation has been explored as a potential HD therapy for decades, with earlier studies using fetal tissue grafts and fetal stem cells suggesting that transplanted cells could survive in the HD brain. However, technical, ethical, and practical challenges limited broader development. Advances in stem cell biology and manufacturing have renewed interest, enabling more standardized cell products with rigorous quality control.
Researchers expect to collect the main data from the study by mid-2028, but participants will continue to be followed for several more years, with the full study expected to conclude in 2031. "This trial may help us move one step closer to a future with available treatments that could potentially slow the progression of Huntington's disease (search)," said Dr. Rajmohan. For now, the HD community watches closely as the first participants begin this pioneering journey into neural stem cell therapy.