Why lecanemab’s success spells the revival of small-molecule Alzheimer’s disease treatments
Unlike bulky biologics, small molecules can make Alzheimer’s treatments cheap, convenient to administer, and widely accessible, experts say
In brief
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 old. You’re telling me that when those two kids are in college, I’m not going to know who they are anymore?’ ” Tanzi recalls. “That hit me pretty hard.”
That night, Tanzi called his friend, the late neurologist Steven Wagner, who had been working on an Alzheimer’s treatment for Bristol Myers Squibb. The treatment candidate had been discontinued because of its side effects. As the friends chatted, Tanzi’s recounting of the woman’s visit renewed Wagner’s determination to try again and spurred Tanzi to join the effort to devise a viable treatment. Tanzi recalls Wagner saying, “We’ve got to do something.”
The pair were well aware of the challenges they faced. Alzheimer’s was incurable. It still is today. But back then, the medical community had no successful drug precedent to go off—no validated disease pathway that guaranteed a druggable target.
Alzheimer’s affects over 6 million people in the US, according to the National Institute on Aging, and more than an estimated 32 million people worldwide (Alzheimer’s Dementia 2022, DOI: 10.1002/alz.12694). To treat the disease, drugmakers need a candidate that is widely accessible and, more importantly, safe. Small molecules, experts say, could check these boxes. In the decades since Tanzi’s meeting, researchers have experimented with several compounds, many of which stumbled in the clinic. But the field has been reenergized by the success of a different sort of compound: the biologic drug lecanemab.
https://cendigitalmagazine.acs.org/2023/03/12/why-lecanemabs-success-spells-the-revival-of-small-molecule-alzheimers-disease-treatments-2/content.html