Huntington's disease is an inherited brain condition that damages nerve cells in the brain. It is progressive and gradually reduces a person's ability to walk, talk, think and communicate. There is no cure for Huntington's and its progress cannot be reversed or slowed down.
There are around 7,000 people living with Huntington’s disease (HD) in the UK.
The disease is caused by a faulty gene on chromosome 4 - the huntingtin gene (HTT) - which is passed down through families. If someone has a parent with the faulty HTT gene, they have a 50/50 chance of inheriting the gene. Everyone with the gene will develop the disease.
HD affects both men and women. Symptoms usually develop when people are between 30 and 50 years old and progress relentlessly over the next 10 to 20 years. Rarely, symptoms develop at a younger age, including in childhood.
Most recently, we have helped fund research at Cardiff University, led by Professor Lesley Jones and Dr Thomas Massey. Their results were published in a paper in Nature Neuroscience in April 2022.
The team assessed medical data from over 7,000 individuals with HD, and then selected almost 700 of those with surprisingly early or late onset symptoms.
Using state-of-the-art genetic sequencing technologies, the researchers were able to identify rare genetic variants that have a large impact on the timing of the onset of symptoms of HD. One gene in particular - FAN1 - harboured numerous variants that can modify HD onset. FAN1 encodes a protein that is important in repairing damaged DNA. The team discovered that many of the FAN1 variants in individuals with HD made FAN1 less effective as a DNA repair protein, potentially providing an explanation of why these people have a much earlier-than-expected onset disease.
These results emphasise how single, rare genetic variants can have a large impact, measured in years, on the timing of onset of HD symptoms. They suggest that by targeting these individual modifier genes with new drugs we might be able to significantly delay the onset of HD in patients. As there are currently no drugs that can slow the onset or progression of HD, any progress in this area would be an exciting step forward.
This research was funded by money raised by Jack May and family. At the age of 18, Jack found out that he has the Huntington's gene. He ran the 2017 London Marathon to raise money for research. Read Jack's story.
Previously funded research includes our funding of PhD student Helen Crawford, at UCL Institute of Neurology. Helen used imaging techniques to examine the structure and state of the brains of Huntington's patients (including 'pre-manifest' patients, who had not yet developed symptoms), compared to healthy controls. Her work has improved understanding of the changes that take place during the early stages of Huntington's, and helps inform strategies to manage and treat the disease.
