Huntington's Disease Gene Therapy Slows Progression by 75% in First Brain Gene Therapy Trial

The Naked Scientists host a discussion with Ed Wilde and Sarah Tabrizi of University College London about Huntington's disease, its genetic basis, and a groundbreaking gene therapy approach. They explain how a CAG repeat expansion drives neurodegeneration, why the brain is particularly vulnerable, and how repeats can grow over a person’s lifetime, shaping when symptoms begin and how quickly they progress.

The conversation then moves to therapeutic strategies, from antisense-like gene-silencing to a brain-delivery gene therapy that uses a virus to turn off the disease-causing message. After years of research, early results show a 75% slowdown in progression in a high-dose group over three years, offering renewed hope for families affected by this inherited disorder.

Overview

The Naked Scientists welcome Ed Wilde, a neuroscientist, and Sarah Tabrizi, a neurologist at University College London, to explore Huntington's disease (HD) — an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. HD typically emerges in midlife, with motor, cognitive and psychiatric symptoms that worsen over time. The guests emphasize the familial nature of HD, noting a 50/50 risk for children of an affected parent and that more than 20% of at-risk individuals opt for predictive genetic testing to learn their status.

They explain how discoveries about the gene and its repeats have transformed HD research, from early brain-behavior observations to understanding how the repeats drive toxic protein production and neural loss. The episode outlines the journey from understanding the disease to attempting therapeutic strategies that directly target the genetic message.

"that repeat grows during your lifetime." - Sarah Tabrizi, neuroscientist and neurologist