Getting drugs to cross the blood-brain barrier can be a problem in treating neurological disorders, but scientists at Duke-NUS Medical School may have found a solution. They have created a molecular model of a transporter that could prove important in the development of therapeutic agents that need to be delivered to the brain.
The blood-brain barrier separates circulating blood fom the central nervous system to prevent entry of both toxins and drugs to the brain, restricting treatment of many brain diseases.
The Mfsd2a transporter modeled by the Duke researchers is a potential conduit for drug delivery directly to the brain, bypassing the barrier.
In this study, recently published in the Journal of Biological Chemistry, first author Duke-NUS MD/PhD student Debra Quek and senior author Professor David Silver used molecular modeling and biochemical analyses of altered Mfsd2a transporters to derive a structural model of human Mfsd2a. Importantly, the work identifies new binding features of the transporter, providing insight into the transport mechanism of Mfsd2a.
“Our study provides the first glimpse into what Mfsd2a looks like and how it might transport essential lipids across the blood-brain barrier,” said Ms Quek. “It also facilitates a structure-guided search and design of scaffolds for drug delivery to the brain via Mfsd2a, or of drugs that can be directly transported by Mfsd2a.”
Currently this information is being used by Duke-NUS researchers to design novel therapeutic agents for direct drug delivery across the blood brain barrier for the treatment of neurological diseases. This initiative by the Centre for Technology and Development (CTeD) at Duke-NUS, is one of many collaborative research efforts aimed at translating Duke-NUS’ research findings into tangible commercial and therapeutic applications for patients.
