The Wyss Institute for Biologically Inspired Engineering at Harvard University announced this week that it is collaborating with multiple industry partners to discover more effective approaches to deliver drugs across the blood-brain barrier (BBB) for the treatment of brain diseases. The main goals of the initiative will be to identify transport target proteins in the BBB and to develop antibody compounds that bind to these targets to facilitate the delivery of future therapeutics to the brain. The pharmaceutical companies Bristol-Myers Squibb Company, U.S.A.; Eisai Inc., Japan; and H. Lundbeck A/S, Denmark; are equally supporting this research effort and will share in the program’s findings to inform their own drug development activities. Through the Massachusetts Life Science Center’s Novel Therapeutics Delivery program, the collaboration was recently awarded a $750,000 grant as additional support.
In additional agreements, the Wyss Institute is collaborating with Cell Signaling Technologies, Inc., U.S.A., to study RNA and protein expression in different tissues in order to identify new BBB transport targets, and with Lundbeck and FairJourney Biologics, a Portugal-based antibody discovery company, to co-develop antibody compounds that would shuttle drugs to the brain via known and novel targets identified in the broader program.
The complementary research agreements, constituting a unique collaboration model for the Wyss Institute, were set in place by Harvard’s Office of Technology Development (OTD).
For the treatment of neurological and neurodegenerative disorders, brain tumors, and many other diseases, transporting therapeutics across the BBB remains a formidable challenge. The capillary vessels, and associated non-neuronal and neuronal cells contacting them on the brain side of the BBB form a highly selective security system that allows nutrients and oxygen to enter the brain from the blood circulation, and waste products including carbon dioxide to be eliminated from the brain. The BBB also actively blocks the entry of pathogens, neurotoxic substances, and most drugs into the brain, including small molecule, antibody, and anti-sense oligonucleotide therapeutics. On average, less than 1% of a drug enters the brain from the bloodstream. The impact of this poor drug transport across the BBB is enormous. For example, in the past decade alone, more than 200 clinical trials of drug candidates for Alzheimer’s disease alone have failed, partly due to poor transport across the BBB resulting in failure to achieve therapeutic drug concentrations in the brain.
The novel pre-competitive initiative began in discussions between James Gorman, principal investigator of the Wyss Institute’s Brain Targeting Program, and Richard Hargreaves, senior vice president and head, Neuroscience Thematic Reseach Center, Bristol-Myers Squibb. “To more effectively treat brain diseases, it is critically important to find better strategies to transport drugs into the brain. However, the complexity of this problem makes it challenging for individual research institutions or companies to solve on their own,” said Hargreaves. “We strongly believe in this type of collaboration to develop tools for drug development and delivery. This collaboration offers a compelling opportunity to discover new approaches for drug delivery to the brain.”