Faculty Bibliography

Background: Anti-LINGO-1 is a monoclonal antibody antagonist of LINGO-1, an oligodendrocyte differentiation and myelination suppressor. Objective: To determine the efficacy/safety of anti-LINGO-1 for CNS remyelination. Methods: Subjects with a first unilateral acute optic neuritis episode were treated with high-dose steroids and randomized to 100mg/kg anti-LINGO-1 IV or placebo every 4 weeks (NCT01721161). Subject and IRB approval were obtained. Nerve conduction latency recovery using full-field visual evoked potential (FF-VEP) in the affected eye over time versus unaffected eye at baseline assessed remyelination (pre-specified primary endpoint). Between-treatment comparisons were evaluated by ANCOVA and mixed-effect model repeated measure (MMRM) in subjects who completed the study and did not miss >1 study dose or receive MS modifying therapy (prespecified per-protocol population). Safety/tolerability was evaluated in those who received >1 study dose and included adverse event (AE) and clinical laboratory result assessments. Results: Anti-LINGO-1-treated subjects (n =33) showed improved latency recovery versus placebo (n=36): mean (95% confidence interval) -7.55ms (-15.12 to 0.01) at Week 24 (P=0.05); -9.13ms (-16.11 to -2.14; P=0.01) at Week 32. 54% of anti-LINGO-1 subjects had no/mild latency delay at Week 24 (affected eye FF-VEP latency <10% worse than baseline fellow eye) versus 27% of the placebo group (P=0.036). Additional subgroup analyses will be presented. 34/41 in each group experienced any AE, serious AEs occurred in 2 placebo and 5 anti-LINGO-1 subjects, and there were 3 treatment-related serious AEs. Conclusions: Improvement in FF-VEP latency is consistent with the first evidence of remyelination in a Phase 2 trial. Anti-LINGO-1 was generally well tolerated

SUMMARY: Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Concussion, a form of mild TBI, might be associated with long-term neurological symptoms. The effects of TBI and concussion are not restricted to cognition and balance. TBI can also affect multiple aspects of vision; mild TBI frequently leads to disruptions in visual functioning, while moderate or severe TBI often causes structural lesions. In patients with mild TBI, there might be abnormalities in saccades, pursuit, convergence, accommodation, and vestibulo-ocular reflex. Moderate and severe TBI might additionally lead to ocular motor palsies, optic neuropathies, and orbital pathologies. Vision-based testing is vital in the management of all forms of TBI and provides a sensitive approach for sideline or post-injury concussion screening. One sideline test, the King-Devick test, uses rapid number naming and has been tested in multiple athlete cohorts.