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Abstract
Biogens anti-LINGO-1 antibody yielded positive results in a phase 2 trial in acute optic neuritis (AON), a relatively rare disease. The realprize for the company will be if the molecule shows activity in multiple sclerosis (MS). Both conditions result in neuronal damage, andAON can be an early symptom of MS. LINGO-1 (leucine-rich repeat and immunoglobulin domain-containing 1), which is expressedonly in neural tissue, prevents remyelinationby complexing with the neurotropin p75NTR and NgR1. By using anti-LINGO-1 to inhibit what is stopping myelination, the hope is to instigate remyelination. (Most MS drugs, such as the companys Avonex (interferon beta-1a) and Tysabri (natalizumab), work by inhibiting demyelination.) In the 82-patient, placebo-controlled clinical trial (RENEW), patients receiving six injections of the drug had a 34% improvement at 24 weeks compared to placebo in nerve conduction velocity, that is, the timeit took for signals to reach the brain from the retina (the primary endpoint). However, there was no improvement in vision and thickness of the optic nerve (secondary endpoints). Although these results indicate repair had occurred,it remains to be seen how it will work in MS, where patients often enter treatment long after the acute phase, when repair is most likely, is over. Results of the companys phase 2 trial in MS (SYNERGY) are expected next year.