Behind the world’s first neural stem cell clinical trial to treat Huntington’s disease

REGEN4HD aims to enroll 21 patients in early stages of the incurable genetic disorder

IN THE NEWS: Huntington’s disease, a fatal and progressive genetic disorder that gradually destroys brain cells, remains one of the most devastating and treatment-resistant neurological conditions with no therapy shown to slow it.

This June, Leslie M. Thompson, PhD, UC Irvine Donald Bren Professor of psychiatry and human behavior and neurobiology and behavior, and Dr. Ravi Rajmohan, a board-certified neurologist UCI Health, launched the world's first neural stem cell clinical trial aimed at slowing the progression of the disease. Rajmohan, Thompson Dr. Jefferson Chen spoke with Neurology Live about the trial.

REGEN4HD is a phase 1b/2a clinical trial evaluating hNSC-01, an embryonic stem cell-derived neural stem cell therapy delivered directly into the brain using MRI-guided stereotactic navigation.

“The rationale for using embryonic stem cell-derived neural stem cells as a treatment is their ability to differentiate into multiple cell types, which may prolong neuron survival and may provide cellular restoration of lost circuitry and replacement of lost cells. This is different than other approaches to transplant.”

“In preclinical studies in Huntington’s disease mouse models, we observed significantly improved disease-relevant outcomes at the behavioral, molecular and electrophysiological levels, cells differentiated into several types of neuronal subtypes and notably produce brain derived neurotrophic factor,” said Thompson.

“If these findings were to be reproducible in humans, this may offer significant benefits to patients by slowing the progression of the disease, by treating its symptoms, or both. This remains to be seen,” said Rajmohan.

Chen spoke about the high precision required for the delivery of cells into the brain.

“The MRI guided stereotactic navigation is key to placing the cells in the caudate and the striatum which are the areas in the brain that are affected by the Huntington's. These targets are just millimeters wide and in some cases millimeters in length. The MRI guidance system that we are using allows us to very precisely place the canula (a long and thin delivery tube) into the targets.”

The trial plans to enroll 21 people with early-stage Huntington’s. The first patient has not reported any serious adverse events.

Thompson is the REGEN4HD clinical trial sponsor. Her research focuses on Huntington's disease, amyotrophic lateral sclerosis, X-linked dystonia-parkinsonism, neurodegenerative disorders, human genetic disorders.

Rajmohan is a UCI Health board-certified neurologist who is fellowship-trained in geriatric neurology (dementia) and movement disorders. He is the REGEN4HD clinical trial principal investigator. He specializes in neurodegenerative disorders such as atypical parkinsonism, Huntington's disease and leukodystrophies. As an assistant clinical professor in the department of neurology at the UC Irvine School of Medicine, his research focuses on observational studies and clinical trials for atypical parkinsonism, Huntington's disease and leukodystrophies.

Chen is a board-certified UCI Health neurosurgeon. who specializes in neurological trauma and critical care, normal pressure hydrocephalus, stroke and brain tumors. He is a leader in such techniques as multimodal brain monitoring for traumatic brain injury and the use of BrainPath® technology to access deep-seated lesions. His research interests include the study of the molecular mechanisms and biochemical underpinnings of traumatic brain injury and stroke, and the flow of fluids through the brain.