New Zealand OKs Phase 1 trial of Huntington’s therapy SRP-1005
Sarepta says trial will evaluate safety, tolerability of under-the-skin injection
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The New Zealand Medicines and Medical Devices Safety Authority (Medsafe) has given Sarepta Therapeutics the go-ahead to start a first-in-human Phase 1 clinical trial of its investigational therapy SRP-1005 for Huntington’s disease.
Sarepta plans to start the trial, dubbed Study SRP-1005-101 or INSIGHTT, between April and June, according to a company press release. It will evaluate the safety and tolerability of the therapy, delivered via an under-the-skin (subcutaneous) injection, in about 24 participants.
Medsafe’s decision comes about a month after Sarepta filed an application with the regulatory agency seeking clearance for the trial.
Huntington’s is caused by a mutation in the HTT gene that results in the production of abnormally long huntingtin protein, which is prone to form toxic clumps in nerve cells. This leads to the dysfunction and death of nerve cells, and consequent motor, cognitive, and behavioral symptoms.
SRP-1005, previously known as ARO-HTT, is designed to stop the production of the mutated form of huntingtin, which is expected to slow Huntington’s progression. It consists of a type of molecule called small interfering RNA (siRNA), engineered to bind to HTT’s messenger RNA. This temporary molecule serves as a template for protein production and targets the messenger RNA for destruction.
Crossing the blood-brain barrier
The experimental treatment contains antibody fragments called monovalent fragment antigen binding, which bind to the transferrin receptor 1 protein in the blood-brain barrier and allow the treatment to enter the central nervous system (CNS, or the brain and spinal cord). The blood-brain barrier is a tight cell layer that prevents microbes, toxins, and large molecules from entering the CNS, which keeps many medications from getting through.
Sarepta believes that SRP-1005’s subcutaneous administration may help achieve consistent, robust delivery into the CNS without saturating the transferrin receptor 1 protein.
Preclinical data have demonstrated that SRP-1005 significantly reduced huntingtin levels in deep brain regions that are pronouncedly affected by Huntington’s.
The therapy was initially developed by Arrowhead Pharmaceuticals using its Targeted RNAi Molecule (TRiM) platform, which develops siRNAs designed to lower the production of disease-driving proteins in specific tissues and cells, including the CNS. In 2024, the company entered an agreement with Sarepta for the exclusive global rights to the treatment’s clinical development.
