Brain-shuttle biologics chart new paths across the blood–brain barrier
Efforts intensify to ferry large-molecule medicines into the brain, following the first FDA approval of an engineered biologic that overcomes delivery hurdles.
For drug developers, the blood–brain barrier (BBB) is more akin to a moat than a membrane. It protects the brain with exquisite selectivity. But in doing so, it keeps out many of medicine’s most powerful therapies: antibodies, enzymes and other biologic drugs that are too large to cross the brain’s specialized vasculature in meaningful amounts.
The US approval of Denali Therapeutics’ tividenofusp alfa (Avlayah) earlier this year marked a turning point in the siege to gain better access to the brain. The first-in-class drug rides a natural transport route into the brain — using the transferrin receptor (TfR) as a molecular ferry — and establishes receptor-mediated brain delivery as a clinically viable therapeutic strategy.
“A Rubicon has been crossed,” says Jim Gorman, head of the brain targeting programme at the Wyss Institute.
Continue reading at Nature Reviews Drug Discovery.
