Fascinating new research from a team at Yale has described a promising new Alzheimer's treatment developed from a half-century old antibiotic. The research suggests a drinkable cocktail composed of newly discovered polymers may disrupt the early stages of the neurodegenerative disease.
The general scientific consensus is that the primary symptoms of Alzheimer's disease are caused by toxic accumulations in the brain of amyloid beta and tau proteins. However, many human clinical trials into drugs designed to break up these toxic plaques have failed, leading some scientists to reconsider their approach.
A team of researchers from Yale decided to zoom in on one of the earliest points in the development of Alzheimer's brain pathology. It was discovered that a compound called cellular prion protein is a vital part of the toxic signaling process associated with amyloid beta plaques, and if the interaction between these two compounds could be disrupted then Alzheimer's could potentially be stopped in its earliest stages.
"We wanted to find molecules that might have a therapeutic effect on this network," explains Stephen Strittmatter, senior author on the new research.
Over 10,000 potential molecules were screened in the hunt for inhibitors and one particular sample significantly stood out. The cephalosporin antibiotic cefixime revealed itself as highly inhibitory, but initial attempts to validate the activity failed, leading the researchers to suspect a degradation product may be responsible.
Subsequent experiments revealed that decomposing the antibiotic over a number of days resulted in the formation of a specific polymer that could pass through the blood-brain barrier and disrupt the interaction between amyloid beta and cellular prion protein. Interestingly, this novel molecule was only found to result from cefixime or ceftazidime and no other cephalosporin antibiotics.
The polymer molecule was optimized, dissolved into a liquid, and tested on Alzheimer's mouse models. The results were promising, with the animals showing remarkable synapse repair and improved memory. The experimental polymer cocktail was also tested on cells modeled to have Creutzfeldt-Jakob Disease, with similar reported success.
The next step for the research is to further optimize the compounds and establish toxicity profiles before there is any transition to human clinical trials. David Reynolds, from Alzheimer's Research UK, is optimistic about these initial results while still cautioning that much more work needs to be done before the treatment is even close to clinical use.
"These promising early results will need to be reproduced in further experiments that also establish the drug's safety profile before it can enter clinical trials to see whether it is effective in people with Alzheimer's disease," says Reynolds.
The new study was published in the journal Cell Reports: https://www.cell.com...secsectitle0020
