Summary: Huntington’s disease is a devastating, universally fatal genetic disorder that systematically destroys nerve cells in the brain, stripping individuals of their motor control, cognitive abilities, and emotional stability. Because symptoms usually manifest during prime adult years (ages 35 to 50) and relentlessly worsen over decades, it places an immense emotional and financial burden on families. Currently, there are no approved treatments capable of stopping or reversing the underlying neurodegeneration.
In a historic medical milestone, UCI Health has launched the world’s first in-human clinical trial utilizing embryonic stem cell-derived neural stem cells to treat Huntington’s disease. The Phase 1b/2a trial evaluates a cutting-edge cell therapy known as hNSC-01.
Delivered via a highly sophisticated, six-hour intra-operative MRI surgical procedure, these specialized cells are implanted directly into the damaged deep structures of the brain. Backed by years of rigorous translational research and a $12 million grant from the California Institute for Regenerative Medicine (CIRM), this trial represents a critical step toward therapies that could finally slow or halt the progression of this relentless disease.
Key Facts
- Historic First-in-Human Trial: This is the first clinical study globally to implant pluripotent embryonic stem cell-derived neural stem cells into human patients suffering from Huntington’s disease.
- The hNSC-01 Therapeutic Target: Preclinical animal models demonstrate that hNSC-01 stem cells protect vulnerable neurons, replace lost cells, rebuild damaged circuits, secretes crucial brain-derived neurotrophic factor (BDNF) proteins, and clear toxic protein aggregates.
- Precision MRI-Guided Delivery: The cells are meticulously mapped and delivered straight into the striatum during a complex six-hour surgery performed entirely within an MRI suite to ensure absolute targeting accuracy.
- Initial Safety Milestone: The first human subject successfully received the neural stem cell transplant at UCI Health – Irvine in May, with no serious adverse events reported to date. A second patient is scheduled for July.
- Trial Cohort & Structure: Managed through the UC Irvine Alpha Clinic, the study will enroll 21 participants (ages 18–65) with early-stage Huntington’s, splitting them into a Phase 1b dose-escalation tier (12 patients) and a Phase 2a expansion tier (9 patients).
Source: UC Irvine
UCI Health, the clinical enterprise of the University of California, Irvine, has opened the world’s first in-human embryonic stem cell-derived clinical trial for Huntington’s disease.
The phase 1b/2a trial will evaluate the safety of hNSC-01 neural stem cells derived from embryonic stem cells which are precisely delivered to the brain by a specialized neurological mapping and targeting stereotactic system and performed in an MRI suite.
The trial is the result of many years of basic and translational science carried out at UCI, and funding by the California Institute of Regenerative Medicine (CIRM), to the research team led by Leslie M. Thompson, Ph.D., Donald Bren Professor of psychiatry and human behavior, as well as neurobiology and behavior, at UC Irvine.
“This clinical trial highlights the important role that an interdisciplinary academic and clinical team together with the HD families, plays in advancing medicine,” said Dr. Thompson, who is 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 first patient received the intervention at UCI Health –– Irvine, home to Orange County’s first adult bone marrow/stem cell transplant and cellular therapy program, in May. UCI Health neurosurgeon Dr. Jefferson W. Chen, assisted by a team including a neurosurgery fellow, delivered the intervention. A second patient is scheduled to receive the intervention in July.
“The first patient intervention went very well. To date, they haven’t reported any serious adverse events,” said UCI Health neurologist Dr. Ravi Rajmohan, the clinical trial’s principal investigator. “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.”
Huntington’s disease is a fatal, progressive genetic disorder that gradually destroys brain cells. It usually begins between the ages of 35 and 50, worsening over 10 to 20 years. Symptoms include involuntary movements, difficulty thinking and planning daily tasks, and mood changes such as depression. If successful, this therapy could prolong independent living and significantly reduce long-term care costs, easing the strain on families.
What intervention is being tested?
The therapy is called hNSC-01. It uses pluripotent neural stem cells derived from embryonic stem cells, which were manufactured through the UC Davis GMP facility, and have been shown in animal studies to:
- Protect existing brain cells
- Replace lost cells
- Rebuild impaired brain circuits
- Release helpful proteins, such as brain-derived neurotrophic factor (BDNF)
- Reduce harmful protein accumulations that damage brain cells
The stem cells were also shown to be safe over long periods in mice.
How is the intervention delivered?
The stem cells are implanted during a roughly six-hour surgical procedure done under general anesthesia. While lying face down in an MRI scanner, the patient receives stem cells implanted directly into the striatum deep in the brain, using a purchased proprietary therapy-enabling platform for navigation and delivery. Damage to the striatum, which is responsible for motor control, decision-making, motivation and more, causes Huntington’s disease symptoms.
Subjects will be closely monitored for safety as well as preliminary signs of potential benefit.
How is the clinical trial funded?
The clinical trial is made possible by a $12 million grant from CIRM, and the trial is coordinated through the UC Irvine Alpha Clinic. It is one of nine CIRM clinical research centers in the state and is the clinical arm of UC Irvine Sue & Bill Gross Stem Cell Research Center.
How many people will the trial enroll?
The clinical trial will enroll 21 people ages 18 to 65 with early-stage Huntington’s disease. Twelve participants will be enrolled into a phase 1b dose-escalation group and nine in a phase 2a expansion group.
How does Huntington’s disease impact patients and families?
As a disease that often progresses over decades, Huntington’s places a huge financial and emotional burden on patients, families and caregivers. In California alone, healthcare costs for Huntington’s patients can range from $3 million to $25 million annually.
Key Questions Answered:
A: The investigational therapy hNSC-01 consists of pluripotent neural stem cells derived from embryonic stem cells and manufactured at the UC Davis GMP facility. In extensive animal models, these cells proved to be remarkably safe over long periods. Rather than just masking symptoms, hNSC-01 is designed to change the physical architecture of the brain. It works through a multi-pronged approach: protecting remaining healthy neurons, physically replacing dead or dying cells, rebuilding broken neural circuits, lowering the accumulation of the toxic genetic proteins that cause the damage, and pumping out protective proteins like brain-derived neurotrophic factor (BDNF).
A: Huntington’s disease primarily attacks the striatum, a critical structural hub buried deep within the brain that regulates motor control, decision-making, and motivation. Delivering stem cells to such a precise, deeply embedded location requires extreme navigational accuracy to avoid damaging surrounding healthy tissue. The six-hour surgery is performed under general anesthesia while the patient is positioned face-down directly inside an intra-operative MRI suite. Neurosurgeons use a proprietary, therapy-enabling navigation platform to continuously visualize the brain’s anatomy in real-time, allowing them to precisely steer and deposit the hNSC-01 cells exactly where they are needed most.
A: Coordinated through the UC Irvine Alpha Clinic and funded by a $12 million CIRM grant, the trial is enrolling a total of 21 participants between the ages of 18 and 65 who have been diagnosed with early-stage Huntington’s disease. The trial is divided into two distinct structural phases: first, a Phase 1b dose-escalation group consisting of 12 participants to meticulously evaluate safety and establish proper dosing thresholds; second, a Phase 2a expansion group of 9 participants to further evaluate safety and capture preliminary signs of clinical efficacy.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this stem cell and Huntington’s disease research news
Author: Jessica Neuman
Source: UCI Health
Contact: Jessica Neuman – UCI Health
Image: The image is credited to Neuroscience News
