Multi-tasking drugs: Researchers develop drug candidates that target multiple disease-causing factors

Tuesday, January 10, 2017

Artistic representation of a brain and neurons.

Byline: Nyasha Gondora, Pharmacy PhD student

Alzheimer's disease claims more lives a year than breast cancer and prostate cancer combined. Current Alzheimer’s drugs on the market have limited effectiveness because they do not treat all of the disease-causing factors. Researchers from Waterloo’s School of Pharmacy are working to develop drug candidates that can target multiple Alzheimer's pathways.

Jonathan Sutley, a Master's candidate in Prof. Praveen Nekkar Rao’s lab, is modifying the structure of phenoselenazine compounds (PSZs) to develop them into multi-targeting Alzheimer's drugs.

The challenge with developing compounds that target all Alzheimer's disease pathways is getting them into the brain.

Developing drugs that target the brain is a challenge because of the blood brain barrier (BBB) - a shielding layer which acts like a gate-keeper to the brain. The BBB is a highly selective and semi-impermeable layer that protects the brain by restricting the entry of foreign substances. Only a limited range of molecules that fit strict criteria are able to bypass the BBB.

The best way to develop drugs that can enter the brain is to modify chemical structures of drugs that are already successful in crossing the blood brain barriers.

Sutley is chemically modifying the PSZ structure to create multi-targeting Alzheimer's drugs. PSZs are derived from the structure of many effective anti-psychotic drugs. This approach will ensure that the developed compounds are able to reach the brain.

These PSZ derivates can treat pathological factors in Alzheimer's, including: the abnormal accumulation of brain proteins, prevent the degradation of molecules essential for communication of brain cells and reduce the production of harsh chemicals in the brain that disrupt its environment.  

Sutley has already synthesized a library of PSZ derivatives and is currently working on increasing the yield of his product. The next steps in Sutley's work would be biochemical and toxicity screening.

Though there is still a long way to go before these compounds can reach the market, there is great hope among scientists that this approach could produce a more effective treatment for Alzheimer's disease.

This research was funded by the Canadian Institutes of Health Research (CIHR–CGS Master’s Program), Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Foundation for Innovation (CFI) and Ministry of Research, Innovation and Science, Government of Ontario.

NOTE: BIOL 690 Scientific Communication is a graduate course that helps students enhance their skills in the acquisition, organization and presentation of scientific information. Students in the course interviewed and wrote a news story about one of their classmates' research.