An Alzheimer's Advance, Not a Cure-All

"A Food and Drug Administration committee meets June 10 to issue a recommendation for donanemab, a drug to treat Alzheimer's disease. As a practicing geriatrician, I often get questions from patients about whether it or other drugs will cure the disease. The answer is that while there's no silver bullet, it is a leap in the right direction.

When exploring how to treat Alzheimer's, it's helpful to remember the lessons of cancer drug development. Sidney Farber in 1947 prescribed aminopterin -- a drug originating from nitrogen mustard used as a chemical weapon in World War II -- for pediatric patients with leukemia. His research was met with skepticism, because while the drug was moderately effective, it was also toxic. Aminopterin was the predecessor of drugs later used in chemotherapy, now a standard of care, along with radiation and immunotherapy.

Like Farber, many researchers have used first-in-class drugs -- those that use a new mechanism to treat a condition -- to improve patient outcomes. This will be the holy grail for Alzheimer's care.

In Alzheimer's patients, abnormal levels of amyloid -- a naturally occurring protein -- disrupt cell function in the brain.

 Removing amyloid can slow cognitive decline by about 30%. Anti-amyloid drugs slow the progression of the disease, granting patients another five or six months of clearer thinking, better function and delay to the next stage of the disease. 

Leqembi was the first drug of this kind to receive traditional FDA approval in 2023. Now, the agency is meeting to consider donanemab, which is similarly designed to clear out amyloid from the brain.

It's important to recognize, however, that treatment isn't so simple. Alzheimer's is characterized by the presence of several misfolded proteins, as well as aging-related impairments, including metabolic disturbances and vascular dysfunction. Because of the disease's complexity, a single drug targeting one pathway won't suffice. 

That's why I support developing drugs targeting the various aging pathways involved in the onset of the disease. Anti-amyloid drugs should become part of the standard of care, but future treatment must include several drugs targeting the underlying pathologies.

In 45 years caring for Alzheimer's patients, I've often seen hopelessness among patients and doctors about the disease and its potential treatments. That despair has started to subside with new drugs in the pipeline, 75% of which target novel pathways.

FDA officials shouldn't let perfection get in the way of progress. Anti-amyloids are fairly safe, modestly effective, and the only disease-modifying drugs currently available. I remain hopeful that this first class of therapeutics is merely a starting point as scientists build out an arsenal of drugs necessary to stop Alzheimer's.

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Dr. Fillit is a co-founder and chief science officer of the Alzheimer's Drug Discovery Foundation." [1]

1. An Alzheimer's Advance, Not a Cure-All. Fillit, Howard.  Wall Street Journal, Eastern edition; New York, N.Y.. 10 June 2024: A.15.