Hope for Alzheimer's patients

Alex Eben Meyer

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Can a drug that targets rogue proteins in the brain help rein in Alzheimer’s disease?

The drug lecanemab, if used early in the course of the disease, may slow down the cognitive decline of memory, judgment, and other key cognitive functions by 27 percent. “The results are unprecedented,” says Christopher van Dyck ’77, a neuroscientist at the Yale School of Medicine and lead author of the study.
 
In Alzheimer’s disease, a protein fragment called amyloid beta accumulates in the spaces between neurons, destroying vital connections that keep memory and other cognitive functions sharp. But as these amyloid roadblocks slow down the brain’s traffic, lecanemab latches on to clear them away.

Previous trials had shown that the drug could reduce amyloid levels in the brain, prompting the FDA to grant accelerated approval. The new trial—phase three, which tests safety and how well a treatment works—adds evidence that patients may also experience cognitive benefits within 18 months. “Most of us from the field thought it was a foregone conclusion that the FDA would give it [accelerated] approval,” says van Dyck. “The real question is what happens with the upcoming traditional approval based on clinical measures.” (Lecanemab is being developed in partnership between Eisai Co. and Biogen.)

One remaining concern about lecanemab is its side effects. A small set of trial participants experienced swelling in the brain, and there are rare reports of fatal brain bleeds, attributed to combining the drug with other medications such as blood thinners.

Van Dyck is now most interested in the benefits of long-term treatment with lecanemab, starting before cognitive decline begins in people with high amyloid. It will be the subject of an ongoing NIH-funded trial. He also thinks lecanemab may have promise for patients with more advanced cognitive decline, although this remains to be tested. The drug won’t reverse preexisting brain damage. But it may pump the brakes on future decline.

“I have been waiting a long time for something like this,” says van Dyck.