ISMB Research could spell new approach to preventing progression of Huntington’s disease

June 2018

New research from scientists at Birkbeck and UCL points the way to a new approach in preventing progression of Huntington’s disease (HD), by manipulating the mutated protein associated with the disease.

HD is an inherited neurodegenerative disease, thought to affect about 7000 people in the UK. There is currently no treatment or cure for the disease, which causes progressive movement disorders and early death.

The disease is caused by a single mutation, which occurs in a gene that encodes the information to make a protein called huntingtin. The mutation causes this protein to form clumps and this process is associated with the damage to brain cells seen in HD. These clumps – or ‘aggregates’ – have been found in the brains of individuals with HD, but it is not clear how they form.

Using a fluorescent tag to track the mutated protein, the researchers found that it can first form a liquid-like cluster that subsequently converts into the harmful aggregates, which are solid and fibrous. Crucially, the researchers showed, both in isolation and in cells, that the aggregates can be easily dissolved when exposed to a chemical called hexanediol when it is in its early liquid-like form – but the chemical does not have any effect once the clusters have ‘solidified’ into aggregates.

Professor Helen Saibil, who led the study, said: “Our findings suggest that the harmful aggregates associated with Huntington’s disease emerge from a form which could be reversible. If the protein behaves similarly in brain cells, it might be possible to target the liquid clusters and prevent the protein from forming the aggregates which are associated with developing Huntington’s. This could have major implications for slowing or preventing disease progression in the future.”

The research formed the PhD project of Dr Tom Peskett (who was a student on the ISMB’s Wellcome Trust PhD programme) and is published in Molecular Cell. It was also the subject of an article in the Evening Standard on 29 June 2018.