(Arthur Toga, UCLA/NIH.gov)
1 March 2018. A medical school professor in Singapore is starting a biotechnology company to discover and develop new drugs for neurological disorders based on his research with mechanisms for crossing the blood-brain barrier. The company Travecta Therapeutics in Singapore is founded by David Silver, professor of cardiac and metabolic disorders at Duke-NUS Medical School.
Silver’s research uncovered mechanisms for natural proteins in the body to cross the blood-brain barrier that usually prevent molecules from crossing from the blood stream into brain cells. Blood vessels in the brain form a support network for brain functions, with tightly-packed cells lining blood vessels that allow nutrients to pass through, but keeping out foreign substances. This barrier also keeps out drugs to treat neurological conditions, such as Parkinson’s or Alzheimer’s disease, and its impaired functioning is also implicated in these disorders. So far, no efficient method is available to penetrate this barrier that prevents some 98 percent of current drugs from reaching the brain or central nervous system.
In his research, Silver discovered the way a natural omega-3 fatty acid, docosahexaenoic acid or DHA, is allowed to cross this barrier. DHA is vital for development of infants’ brains, and found in breast milk, but is otherwise not made in the body. In addition, DHA needs to be first metabolized in the liver, where it joins with lysophosphatidylcholine, or LPC, a compound that enables DHA molecules to cross the blood-brain barrier. Yet, DHA linked to LPC is still missing a key ingredient: a transporter protein called Mfsd2a to take DHA-LPC into the brain itself, which is Silver’s main discovery.
Travecta Therapeutics is licensing and plans to build on Silver’s discoveries to design and develop in preclinical stages new drugs that cross the blood-brain barrier. The therapies would take the form of LPC-drug conjugates or combinations that are linked to Mfsd2a. The discovery process is expected to produce compounds optimized for transport across the blood-brain barrier, and evolve into a platform for further drug discoveries. For drug development, the company is anticipating creating lab cultures with human-derived cells over-expressing Mfsd2a, as well as mice genetically engineered to knock-out genes producing Mfsd2a.
Silver is joined by Mahmood Ahmed as a scientific founder of Travecta Therapeutics. Ahmed is a 14-year pharmaceutical industry veteran and an expert at developing drugs for central nervous system disorders. Michael Schleifer and Laurent Benissan are also founders of Travecta, bringing their start-up business experience from Sprim, a global health care consultancy with offices in Singapore. Travecta is financed by TKS I, an investment fund for health care and life science start-ups, backed by Tikehau Capital in Singapore.
Travecta is not Silver’s first spin-off enterprise from Duke-NUS. As reported in Science and Enterprise in May 2017, Silver, with Schleifer and Benissan started Babynostics, licensing Silver’s research to develop a new food product for mothers to help a baby’s cognitive development. Babynostics is also based on Silver’s research with DHA and Mfsd2a.
In the following video, Silver tells more about his work with the blood-brain barrier.
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