CAMBRIDGE, Mass. — Sarepta Therapeutics announced the submission of a clinical trial application for SRP-1005, an investigational treatment for Huntington’s disease, to Medsafe, the New Zealand Medicines and Medical Devices Safety Authority. The application covers Study SRP-1005-101, also known as INSIGHTT, a first-in-human clinical trial that the company expects to initiate in the second quarter of 2026, pending regulatory approval.
SRP-1005, formerly known as ARO-HTT, is an investigational small interfering RNA therapeutic designed to reduce the production of the huntingtin protein that causes Huntington’s disease. The therapy is administered subcutaneously and is intended to reach deep brain regions involved in disease progression.
“Huntington’s disease is a devastating, progressive condition with extremely limited therapeutic options and no approved treatments to slow or halt its course. Families carry the burden across generations, and the need for new approaches is urgent,” said Louise Rodino-Klapac, Ph.D., president of research and development and technical operations at Sarepta. “SRP-1005, a subcutaneously dosed siRNA therapy intended to target the deep brain and knock down the protein that causes Huntington’s disease, represents a novel and potentially paradigm changing approach to the treatment of this devastating disease.”
INSIGHTT is a Phase 1, multi-center, dose-escalation study designed to evaluate the safety and tolerability of subcutaneous dosing of SRP-1005 in approximately 24 participants. The investigational therapy uses an advanced transferrin receptor protein 1 targeting approach with a monovalent fragment antigen binding design to support efficient delivery to the central nervous system. Subcutaneous administration is intended to remain below transferrin saturation while enabling sustained and effective penetration across the blood-brain barrier.
In preclinical studies, SRP-1005 demonstrated the potential for significant reduction of huntingtin protein levels in key deep brain regions, including the putamen and caudate, as well as in the temporal and frontal cortices.
Huntington’s disease is a rare, inherited neurodegenerative disorder caused by a mutation in the gene that encodes the huntingtin protein. The disease leads to progressive deterioration of nerve cells in the brain, resulting in cognitive decline, movement disorders, and behavioral changes. In the United States, approximately 40,000 people are living with symptomatic Huntington’s disease, and an estimated 200,000 additional individuals carry the genetic mutation and are at risk of developing symptoms. The condition typically manifests between the ages of 30 and 50 and worsens over time. Each child of an affected parent has a 50% chance of inheriting the mutation, and there are currently no approved disease-modifying treatments that address the underlying cause.
