Precision medicine offers a glimmer of hope for Alzheimer’s disease
The decades-long search for effective ways to treat or prevent Alzheimer’s disease is littered with failures, leaving 5.7 million Americans already stricken with this form of dementia without a lifeline. The rest of us are left to hope we won’t be among the 1 in 10 over 65 who gets the devastating diagnosis.
But precision medicine—an approach that is changing the treatment of cancer and spawning targeted therapies for a wide range of diseases—may open new avenues for the treatment of Alzheimer’s disease. And new ways to test experimental treatments promise to more quickly identify treatments that work, and perhaps the patients in whom they will work best.
During the week of July 23, dementia specialists gathered at the Alzheimer’s Assn.’s International Conference in Chicago to assess the state of the field. And researchers gleaned some glimmers of real hope in both precision medicine and innovative trial designs to deliver new treatments for Alzheimer’s disease.
These approaches raised expectations that at least two experimental drugs—one called BAN2401 and the other Anavex 2-73—might successfully treat some with Alzheimer’s.
In the case of BAN2401, the successful preliminary finding of a trial that enrolled 856 patients with early Alzheimer’s disease has breathed new life into a hypothesis that persists despite withering failures: That reducing clumps of proteins called amyloid plaques that accumulate in the brains of those with Alzheimer’s might slow or reverse their symptoms of memory loss and cognitive confusion.
Using an innovative clinical trial design, the U.S. and Japanese companies developing BAN2401 found that over 18 months of treatment, patients who got the highest doses of the medication had dramatic reductions in amyloid plaque deposits in their brains. And compared with subjects who got a placebo, those who got the highest dose showed a 26% slowing of clinical decline after 18 months.
As the trial of BAN2401 progressed, its “adaptive design” ensured that when new subjects were recruited, they were more likely to be assigned to arms of the trial that showed the greatest promise. While considered controversial by some researchers, clinical trial designs that flex to seize upon promising preliminary findings have a high-level supporter in the Trump administration’s Food and Drug Administration: Commissioner Scott Gottlieb.
In a first-ever bid to apply the principles of precision medicine to Alzheimer’s disease, researchers also reported this week on a small study of Alzheimer’s patients who bear a few “actionable genetic variants.” In these patients, they found, Anavex 2-73 appeared to slow and perhaps even reverse early cognitive decline.
The new findings emerged from a clinical trial designed to test the safety of Anavex 2-73, and it involved just 32 patients with mild to moderate Alzheimer’s. So it’s far too early to tout the success of this experimental drug.
But researchers built an extra step into their safety trial: sequencing the subjects’ genomes. In doing so, they hoped to find genomic signatures in some patients that would make them more likely to respond positively to the drug.
