Small molecules reenter the ring in the quest to treat Alzheimer’s disease

Abstract

The clinical success of the Alzheimer’s disease antibody lecanemab paves the way for the revival of small molecules that similarly promise to keep the brain plaque-free. Cheaper to manufacture and administer than biologics, the drugs could make it practical for patients to start their regimen early in the disease progression, which researchers say is the only way to reap the full benefits of an antiamyloid treatment strategy. In 1999, a woman visited the office of neuroscientist Rudolph Tanzi of Massachusetts General Hospital and Harvard Medical School. She was in her early 30s, seemingly in good health. But she had learned that her mother carried a genetic mutation that predisposed her to Alzheimer’s disease. By the time the mother had reached 45, the disease had ravaged her brain. Tanzi explained to his visitor that she likely inherited the same genetic marker. “She said, ‘I have two kids, 5 and 6 years