Insights in Neurosurgery

Blocking the LINGO-1 pathway as a novel therapeutic approach for CNS remyelination and repair: From discovery to clinical trials

4^th International Conference on BRAIN DISORDERS AND DEMENTIA CARE
August 14-16, 2017 | Toronto, Canada

Sha Mi

Biogen, USA

Posters & Accepted Abstracts: Neurosurg

DOI: 10.21767/2471-9633-C1-006

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 upregulated 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. Opicinumab (anti-LINGO-1) is the first anti-LINGO-1 antibody 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 100 mg/kg. In the Phase II Renew trial, compared with placebo, participants treated with opicinumab showed improved optic nerve conduction latency (measured by full-field visual evoked potential), and indicative of remyelination. In the phase 2b SYNERGY (active relapsing MS trial), an inverted U-shaped dose response was seen in SYNERGY suggesting a clinical effect of opicinumab.