Research carried in part at the ULg has opened the path to a better understanding of the role of Huntingtin during brain development and the division of cortical progenitors in particular. When it is mutated this protein is responsible for Huntington’s disease. These advances are the subject of a publication in NEURON (1).

Once going under the name of St Vitus Dance, Huntington’s Disease is still far from having delivered up all its secrets. But over the last couple of dozens of years or so, more pointed research has enabled the disease to be better understood. We know for example that it is a genetic disease and that it affects a precise area of the brain, the striatum. There it brings about the degeneration of neurons before affecting those of the cortex. This disease is characterized by uncontrolled gestures, dementia and leads implacably to death within around twenty years, most often due to heart failure or suffocation, the patient being unable to control swallowing anymore. Huntington’s Disease results from the mutation of a gene coding for an ubiquitous protein, the Huntingtin. This mutation provokes an expansion in the repetition of CAG trinucleotide, coding for glutamine. ‘A healthy individual has in their gene a series of 10 to 30 CAG,’ explains Juliette Godin, who is carrying out postdoctoral research at Dr Nguyen’s laboratory at the University of Liège’s GIGA-Neurosciences unit. ‘When the protein is mutated, the number of repetitions is greater and can at times exceed 70 and bring about juvenile forms of the disease. The protein thus gains in toxicity and loses in functionality. The longer the repetition is, the earlier the symptoms develop, and the greater is the disease’s impact. There remain nonetheless several grey areas. We do not know why it only affects the neurons of the striatum, for example, whilst it affects a protein present in each of the body’s cells. Nor do we know why the disease is triggered several years after birth, on average at the age of 35, whilst the protein has mutated since birth.’

The disease affects around 1 person in 10,000, with a certain consistency in the different regions of the world. Given the fatal nature of the disease, its dominant transmission could dissuade the people affected from having descendents. Unfortunately it is often activated too late. For families at risk it is possible to establish a pre-implantation genetic diagnosis. ‘But a lot of people choose not to have the test. They know, given their genetic heritage, that they will be potentially ill, but prefer to live in ignorance.’