Arrowhead Pharmaceuticals said on October 14, 2026, that its investigational drug ARO-MAPT reduced total tau protein in the cerebrospinal fluid of healthy volunteers by a mean of 73 percent, with one participant showing an 85 percent drop, 105 days after the final dose. The company, in a press release and in filings tied to the registered trial (NCT07221344), described the result as the first clinical validation of its TRiM delivery system carrying a small interfering RNA molecule across the blood-brain barrier after a subcutaneous injection.
The Phase 1/2a study is a placebo-controlled, dose-escalating trial sponsored by Arrowhead, enrolling up to 64 healthy volunteers and up to 48 people with early Alzheimer's disease, defined as mild cognitive impairment or mild dementia due to Alzheimer's. In the portion reported so far, participants received subcutaneous ARO-MAPT at 2.1 milligrams per kilogram or 6.4 mg/kg on days 1, 8 and 15, or 12.8 mg/kg on days 1 and 15; mean tau reductions at day 105 were 40 percent, 69 percent and 73 percent at those respective doses. ARO-MAPT works by silencing the MAPT gene that codes for tau, a mechanism distinct from the monoclonal antibodies against tau, such as Eli Lilly's E2814, that are also in clinical testing for Alzheimer's disease and related tauopathies.
The findings reported are limited to a fluid biomarker measured in people without Alzheimer's disease, not to tau tangles in the brain, cognition, or disease progression. Arrowhead said treatment was generally well tolerated, with most side effects classified as mild and no serious adverse events, deaths, or discontinuations reported in this interim look. The company said it is continuing to enroll the separate cohort of people with early Alzheimer's disease within the same study, with data from those patients expected in 2027.