Scientists have discovered that subtle brain changes in Huntington’s disease begin approximately twenty years before patients show noticeable symptoms, opening a potential window for early intervention in this devastating genetic condition. The finding could transform how doctors approach treatment of the currently incurable disease.
The research, published in Nature Medicine by scientists at University College London (UCL) and partner institutions, reveals that while cognitive and motor functions remain normal, the brain undergoes detectable changes long before clinical diagnosis.
“Our study underpins the importance of somatic CAG repeat expansion driving the earliest neuropathological changes of the disease in living humans with the Huntington’s disease gene expansion,” says lead author Professor Sarah Tabrizi of UCL Huntington’s Disease Research Centre.
Early Warning Signs
The research team studied 57 people carrying the Huntington’s gene expansion who were, on average, 23 years away from their predicted age of clinical diagnosis. Over approximately five years, they compared these individuals to 46 control participants matched for age, sex, and education level.
Using advanced imaging, blood analysis, and spinal fluid testing, the scientists identified elevated levels of specific proteins indicating neuronal injury, along with reduced levels of other proteins that reflect changes in the brain’s response to neurodegeneration.
Crucially, while these biological changes were occurring, study participants showed no decline in thinking, movement, or behavior compared to the control group.
A Treatment Window Opens
The findings suggest there may be a decades-long period before symptoms appear when future treatments could potentially prevent or delay the onset of the disease. This is particularly significant as Huntington’s disease is genetic, with children of affected parents having a 50% chance of inheriting the condition.
“These findings pave the way for future preventative clinical trials,” explains Dr. Rachael Scahill, co-first author of the study. “This unique cohort provides us with unprecedented insights into the very earliest disease processes prior to the appearance of clinical symptoms, which has implications not only for Huntington’s disease but for other neurodegenerative conditions.”
Looking Ahead
The research team anticipates that clinical trials aimed at preventing Huntington’s disease could become a reality within the next few years. Their work has identified robust markers of early disease progression that could be used to monitor the effectiveness of future treatments.
For the 5-10 people per 100,000 worldwide affected by Huntington’s disease, these findings offer hope that intervention might one day be possible long before the disease begins to affect daily life. The research also provides a model for studying other neurodegenerative conditions, potentially opening new avenues for early detection and treatment of diseases like Alzheimer’s.
Professor Tabrizi acknowledged the dedication of study participants over the five-year period, noting that their commitment may help make preventative clinical trials for Huntington’s disease a reality in the coming years.