Huntington's Disease (HD) Models

Huntington's disease (HD), also referred to as Huntington's chorea, is a rare autosomal dominant neurodegenerative disorder primarily affecting the basal ganglia. It predominantly manifests in middle-aged and elderly populations, characterized by a slow but progressive deterioration that ultimately leads to mortality. The disease is triggered by mutations in the huntingtin gene (HTT), situated on the short arm of chromosome 4. This gene harbors a polymorphic trinucleotide repeat expansion, specifically, CAG repeats (cytosine-adenine-guanine). An excessive number of these CAG repeats leads to the formation of an elongated polyglutamine tract (polyQ tract). When the CAG repeats surpass 40, an abnormal amplification of glutamines occurs in the polyQ region. This results in the misfolding of HTT protein fragments, which subsequently interact with numerous proteins and accumulate in the nucleus and nerve terminals. Such accumulations cause significant neuronal damage and impact extensive regions of the brain.

Despite the elucidation of HD's genetic pathogenesis in 1993, there remains a lack of effective treatments capable of halting the disease's progression.

GemPharmatech has developed the B6-hHTT CAG130 model, in which the N-terminal of human HTT gene with 130 consecutive CAG repeats was introduced into the mouse genome. This model can simulate some key clinical symptoms and dysfunctional phenotypes of HD to help assess the efficacy and safety of potential HD therapies.