Arrowhead's RNAi drug reduces Alzheimer’s‑linked tau protein in early trials

Arrowhead Pharmaceuticals tested its experimental RNAi drug, ARO‑MAPT, in a small safety study of 64 healthy adults. Participants received either 2.1, 6.4 or 12.8 mg per kilogram of body weight in two subcutaneous shots spaced two weeks apart. The highest dose lowered the brain‑associated protein tau by an average of 73% after 105 days, with some volunteers seeing a reduction as high as 85%. Side effects were mild and included bruising at the injection site, respiratory infections and headaches.

Tau protein builds up in the brains of people with Alzheimer’s and may contribute to memory loss, so reducing it is a promising strategy. Existing drugs such as Aduhelm, Leqembi and Kisunla mainly target amyloid beta, another protein that clumps in the brain, and they have limited benefits and safety warnings. ARO‑MAPT uses RNA interference to silence the gene that makes tau in the central nervous system, a method that may bypass the blood‑brain barrier that has hampered other treatments.

The trial was an early‑stage safety study, but the results give clinical proof that the drug can reach brain cells. Arrowhead plans to enroll people with mild Alzheimer’s and up to five injections in a follow‑up study to see if the protein reduction translates into slowed disease progression. The company also aims to test ARO‑MAPT in other tau‑related disorders such as frontotemporal dementia and progressive supranuclear palsy.