Arrowhead Pharmaceuticals has announced interim results from an ongoing phase 1/2a study of ARO-MAPT, the company’s investigational RNA interference (RNAi) therapeutic being developed as a potential treatment for Alzheimer’s Disease (AD) and other tauopathies.

These results represent the first successful clinical validation of a platform to deliver siRNA across the blood-brain barrier and achieve substantial target gene knockdown in the brain. In healthy volunteers, subcutaneous administration of ARO-MAPT achieved deep and durable reductions in cerebrospinal fluid (CSF) total tau, with a mean reduction of up to 73 percent at day 105 and a maximum reduction of 85 percent.

Christopher Anzalone, PhD, President and Chief Executive Officer, Arrowhead Phaarmaceuticals, said, “These early clinical data are exciting because they demonstrate that ARO-MAPT can achieve deep and durable reductions of tau expression in the brain following a simple subcutaneous administration, representing an important step toward developing a potential treatment for Alzheimer’s Disease and other primary tauopathies. Abnormal tau accumulation is a key feature of multiple devastating diseases, and we believe reducing tau production has the potential to offer a meaningful new approach for patients. Equally important, these results provide clinical validation of our proprietary Targeted RNAi Molecule (TRiMTM) delivery platform to potentially address multiple diseases in the Central Nervous System (CNS). This major scientific breakthrough further solidifies Arrowhead’s position as the leading innovator in siRNA therapies.”

ARO-MAPT is designed to silence expression of the Microtubule-Associated Protein Tau (MAPT) gene in the Central Nervous System (CNS), reducing production of all 6 isoforms of the tau protein. Pathological aggregation of tau is implicated in a group of neurodegenerative diseases called tauopathies, which include AD, MAPT-related frontotemporal dementia, and Progressive Supranuclear Palsy.