BBB Hunter agent nears FDA decision

Denali Therapeutics’ enzyme therapy for Hunter syndrome (mucopolysaccharidosis II, or MPSII), capable of crossing the blood-brain barrier (BBB), awaits a decision from the U.S. Food and Drug Administration (FDA) on April 5, 2026. MPSII is a rare, progressive, life-threatening X-linked recessive disease caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). Those who inherit this deficiency develop dysfunction of cells, tissues and organs caused by the accumulation of glycosaminoglycans, including heparan sulfate, which is used as a marker.

Takeda’s Elaprase (idursulfase) is an FDA-approved enzyme replacement therapy for MPSII that provides IDS, but the molecule is too large to cross the BBB and fails to treat the progressive neurological effects caused by the accumulation of glycosaminoglycans in brain cells.