Huntington's disease is an inherited neurological disease caused by an GAC expansion of the gene encoding a protein called huntingtin. It is transmitted in an autosomal dominant mode. In other words, inheriting the mutated copy of the Huntingtin gene (HTT gene) is enough to develop Huntington’s disease. The probability of a sick person passing on the expansion to their children is 50% with a high risk of developing symptoms during their adult life.
The causes of Huntington's disease
The expansion consists of an abnormal repetition of a triplet of CAG nucleotides in DNA at chromosome 4. A copy of the protein becomes abnormal, probably toxic to cells when the number of CAG repeats is greater than 35. The huntingtin protein, whose essential role is to allow neurons to survive, is not enough to prevent the disease from occurring. The parts affected by atrophy during the disease are the cortex and striatum, brain areas involved in motor, cognitive and behavioural functions.
Huntington's disease affects the cortex and striatum, which are involved in motor, cognitive and behavioural functions.
At Paris Brain Institute
The study of the asymptomatic phase of Huntington’s disease is a major focus of the team “Basic and Translational Neurogenetics” co-led by Prof. Alexandra Durr. Huntington’s disease patients were born with the expansion, yet they do not develop symptoms until decades later. What happens in the meantime?
Active collaboration between the clinician-researcher and Dr Sandrine Humbert at the GIN in Grenoble has shown that cerebral anomalies were already present in the foetus. However, the disease does not manifest itself from birth.
There are therefore signs of cellular damage in the foetus, but no clinical damage in children and adolescents, and clinical signs appear in adulthood. There therefore appears to be transient compensation for the deficits. The aim of Alexandra Durr's team is to understand the mechanisms involved during the non-symptomatic period of the disease, in the hope of activating compensatory processes to delay the onset of the disease.
