Huntington’s disease (HD) is an autosomal dominant disorder caused by an expanded CAG repeat in the HTT gene. More than 35 CAGs in the repeat will result in HD. The mutation results in an increase in the length polyglutamine tract at the amino-terminal end of the huntingtin protein. This polyglutamine expansion results in the accumulation of cytoplasmic and nuclear aggregates in neurons, and these aggregates play a central role in the disease. The major neuropathology in HD occurs in the striatum and cerebral cortex but degeneration is seen throughout the brain as the disease progresses. There is currently no therapy available for HD.
In the Neuro-D group we use a range of disease models including iPSC from HD patients to create 2D neurons in a dish and sophisticated 3D brain organoid models, and HD transgenic mice.
We use these models to study HD pathology, investigate affected cell types, and test potential antisense oligonucleotide (AON)-based therapies.
Figure: The major area of the brain affected in Huntington disease is the striatum. The expanded CAG repeat in the HTT gene causes the mutant huntingtin protein to aggregate and these protein aggregates are a hallmark of the disease.