Researchers have identified a drinkable cocktail of designer molecules that interferes with a crucial first step of Alzheimer’s disease and even restores memories in mice.
The binding of amyloid beta peptides to prion proteins triggers a cascade of devastating events in the progression of Alzheimer’s—accumulation of plaques, a destructive immune system response, and synapse damage.
“We wanted to find molecules that might have a therapeutic effect on this network,” says Stephen Strittmatter, professor of neurology and of neuroscience, and director of the Yale University Alzheimer Disease Research Center.
Strittmatter and research scientist Erik Gunther screened tens of thousands of compounds looking for molecules that might interfere with the damaging prion protein interaction with amyloid beta.
As reported in Cell Reports, an old antibiotic looked like a promising candidate but was only active after decomposing to form a polymer. Related small polymers retained the benefit and also managed to pass through the blood-brain barrier.
The researchers then dissolved the optimized polymeric compound and fed it to mice engineered to have a condition that mimics Alzheimer’s. They found that synapses in the brains were repaired and mice recovered lost memory.
A collaborating team at Dartmouth University reported a positive response when they delivered the same cocktail to cells modeled to have Creutzfeldt-Jakob Disease, a devastating neurological condition that infection with misfolded prion proteins causes.
The next step is to verify the compounds aren’t toxic in preparation for translation to clinical trials for Alzheimer’s disease.
Grants from the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, the Alzheimer’s Association, and the Falk Medical Research Trust to Strittmatter funded the work.
Source: Yale University