HD - Huntington Disease

HD is caused by expansion of an unstable trinucleotide repeat (CAG) in the 5’ region of the HTT gene. The continuous expression of the resulting mutant huntingtin protein with an expanded stretch of glutamine in neuronal cells eventually gives rise to cell death, especially in the frontal lobes and the basal ganglia (mainly in the caudate nucleus). The severity of the disease is generally proportional to the number of extra residues. Using Prosensa’s RNA-modulating therapeutics, cellular levels of aberrantly expanded HTT mRNA and mutant huntingtin protein can be reduced.

HD is encountered throughout the world and in all ethnic groups. Global prevalence of HD is estimated to be four to five per one million people. In western countries it is estimated to be eight to ten per 100,000 people. There is no gender predominance. HD usually begins between the ages of 30 to 50 and leads to death 15 to 20 years after onset of neurological impairment. An early-onset variant exists (juvenile HD or Westphal variant) and typically begins in adolescence and with motor features, predominantly slowness of movement (bradykinesia) and increased muscular tone (rigidity type). It presents a more severe course with an average survival time of five to ten years. No effective cure for HD exists.