More options for Huntington’s

The Neuro will conduct four clinical trials on this rare disease this year, more than any other site in Quebec

July 7, 2026 || by Sophie Lorenzo

“Individuals with a rare disease face a condition that has very few treatment options – if any at all.  It is essential that we continue to expand our knowledge of these diseases to be able to develop effective approaches. And patients deserve the opportunity to access emerging therapies,’’ explains Massimo Pandolfo, MD, a neurologist and geneticist specializing in rare movement disorders and the medical director of Clinical Research Unit at The Neuro (Montreal Neurological Institute-Hospital).

Huntington’s Disease is a progressive neurological condition that is sometimes referred to as a cross between schizophrenia, Alzheimer’s and Parkinson’s. It strikes in the prime of life and leads to a crushing decline with emotional, cognitive and physical impairments. There are no effective treatments to slow or stop the disease.

As a leader in neurological research, The Neuro will conduct four clinical trials for Huntington’s Disease this year — more than any other site in Quebec.

When DNA loses its way

Huntington’s disease is caused by a mutation in the HTT gene, which provides the instructions for making a protein called huntingtin. Everyone has a short stretch of DNA in this gene where the three-letter sequence CAG is repeated multiple times. In people with Huntington’s disease, this CAG sequence is repeated many more times than normal.

These extra repeats cause the huntingtin protein to be made with an abnormally long segment, making it prone to misfolding and forming toxic clumps inside nerve cells. Over time, these clumps damage and kill neurons, particularly in brain regions that control movement, thinking, and emotions, leading to the progressive symptoms of the disease.

“Currently, healthcare teams use medication to treat the depression, the psychiatric issues, and decrease the involuntary movements,” says Pandolfo. “But ideally we would target the genetic defect that causes this debilitating disease.”

Identifying genetic signatures

Among the studies offered at The Neuro’s Clinical Research Unit is an important observational project designed to support the development of more precise genetic therapies for Huntington’s disease.

Researchers are identifying naturally occurring genetic “signatures” that are inherited together with the disease-causing HTT mutation. These signatures could allow future treatments to selectively switch off the harmful copy of the gene while leaving the healthy copy unaffected. Because Huntington’s disease is a rare disorder, every participant makes a valuable contribution to advancing research.

“This study will help us identify genetic signatures linked to each participant’s disease-causing HTT mutation. Researchers are developing therapies designed to silence only the mutated copy of the gene while preserving the normal copy. Identifying the most common genetic signatures associated with the mutation is a crucial first step toward making these highly targeted treatments possible” explains Pandolfo.

Targeting faulty RNA

Another clinical trial at The Neuro is evaluating whether an oral treatment can slow the progression of Huntington’s Disease by reducing the production of the harmful huntingtin protein. The treatment works by modifying how the HTT gene’s RNA message is processed, causing it to be broken down before it can be used to make the disease-causing protein.

In an earlier Phase 2 clinical trial, the treatment was found to be safe and well tolerated, and it significantly reduced levels of mutant huntingtin protein. Follow-up over 24 months also suggested a dose-dependent slowing of disease progression. The new trial will assess the treatment’s safety and effectiveness in a larger number of participants.

For more about studies on Huntington’s Disease at The Neuro’s Clinical Research Unit, visit cru.mcgill.ca/mvtdisorders, contact mvt.neurocru@mcgill.ca; (514) 398-5500.