Huntington's Disease

ALN-HTT: Huntington's Disease

ALN-HTT, an RNAi therapeutic for the treatment of Huntington's disease, is designed to silence the huntingtin gene, which is the cause of Huntington's when expressed as a toxic mutated protein.

In September 2009, pre-clinical research, performed in collaboration with Professor Don M. Gash's laboratory at the University of Kentucky College of Medicine, demonstrated that a small interfering RNA (siRNA) targeting the huntingtin gene achieves broad distribution in the CNS following continuous direct CNS administration. Further, direct delivery to the CNS resulted in robust silencing of the huntingtin gene mRNA, extending previously presented pre-clinical data. This silencing effect was achieved at substantial distances from the infusion site, an important step towards translating this delivery approach from animal models to the larger human brain. Additional pre-clinical studies showed ALN-HTT to be well tolerated following continuous direct CNS administration over a period of approximately one month.

Earlier pre-clinical studies also showed that silencing the huntingtin gene translated into a therapeutic effect in animal models, including improvement in motor behavior, which is a hallmark of this debilitating and fatal disease. The RNAi therapeutic reduced expression of mutant huntingtin in the brain and sustained a benefit in motor behavior for at least one week.

ALN-HTT is being developed in collaboration with Medtronic, a company which has unmatched expertise in delivering therapeutics directly to the central nervous system, where we aim to develop a drug-device combination product.

ALN-HTT Clinical Timeline