Sha Mi
Biogen, USA
Title: Blocking LINGO-1 for CNS Remyelination and Repair: From Discovery to Clinical Trials
Biography
Biography: Sha Mi
Abstract
• LINGO-1 is a Leucine rich repeat, Ig domain containing, Nogo receptor interactive protein that is selectively expressed in CNS oligodendrocytes and neurons. Its expression is developmentally regulated, as well as up-regulated in CNS diseases and spinal cord injury. LINGO-1 negatively regulates oligodendrocyte differentiation and myelination, neuronal survival and axonal regeneration by activating RhoA and inhibiting ATK phosphorylation. Across diverse animal CNS disease models, targeted LINGO-1 inhibition promotes neuron and oligodendrocyte survival, axon regeneration, oligodendrocyte differentiation, remyelination and functional recovery. The targeted inhibition of LINGO-1 therefore represents a novel approach for the treatment of neurological diseases. BIIB033 is the first anti-LINGO-1 anti-body to enter clinical development for CNS repair. The Phase I study found anti-LINGO-1 to be safe and well tolerated up to the maximum planned dose of 100mg/kg. BIIB033 is currently being evaluated in Phase II clinical study for the treatment of RRMS and SPMS
