Results from a single\center academic study with phenytoin that enrolled within 14?days of AON onset suggest that treatment with candidate RGCL protective brokers could be initiated earlier after onset of AON symptoms.23 The apparent lack of influence of visual impairment and brain Rafoxanide MRI data in stratifying patients according to VEP latency prolongation at week 24 is noteworthy. the efficacy/security of opicinumab versus placebo in participants with a first unilateral acute optic neuritis (AON) episode. Difference in visual evoked potential (VEP) latency of the affected vision at 24?weeks versus the fellow vision at baseline was the primary endpoint. Interactions between the main endpoint and prespecified baseline variables (including age, timing of treatment initiation, and visual impairment) using the median as Rafoxanide slice\off were evaluated in the per protocol population using analysis of covariance (ANCOVA); subgroups based on preexisting brain T2 lesion volume were also analyzed. Interactions between the main endpoint and retinal ganglion cell layer/inner plexiform layer (RGCL/IPL) and retinal nerve fiber layer (RNFL) thickness were assessed post hoc as was weight gain by treatment. Results Treatment benefit of opicinumab (values due to the small sample size of the RENEW study. In fact, the primary endpoint of RENEW was not itself powered for statistical significance.11 Among all subgroups analyzed, the greatest VEP latency recovery was observed in the older half of participants treated with opicinumab in the PP population (baseline age 33?years), while the worst latency delay was observed in the older participants treated with placebo. The younger half ( 33?years of age) experienced similar and intermediate degrees of recovery in the two treatment arms. The finding that older placebo\treated participants experienced worse VEP latency recovery is usually consistent with the biological concept that spontaneous remyelination is usually negatively affected by aging.17, 18, 19, 20, 21 That this strongest opicinumab treatment effect was observed in this subgroup, suggests that LINGO\1 blockade may be more effective in individuals whose initial clinical episode of CNS demyelination occurs at an older age. Results from a Phase 2 trial showing a modest reduction in VEP latency in patients (mean age?=?40.1?years) with relapsing MS with preexisting optic neuritis and good preservation of the RNFL treated with clemastine fumarate are consistent with this getting.22 The hypothesis that older individuals with AON may be more responsive to LINGO\1 blockade with opicinumab could be explained by one or more of the following reasons. First, more youthful participants may have greater inherent recovery potential and spontaneous remyelination, which may dampen any therapeutic effect of opicinumab; conversely, intrinsic remyelination may be weaker in older participants, with a greater margin for therapeutic enhancement in this subgroup.21 Second, younger participants may be less responsive to opicinumab because increased LINGO\1 expression may not play a role in the lack of spontaneous remyelination. Third, more youthful participants are more likely to have active disease activity (even asymptomatic MS) compared with older patients, confounding any beneficial treatment effect of reparative candidate treatments such as opicinumab. Fourth, the initial demyelination may be more severe in the older participants making it unlikely for spontaneous remyelination to be clinically meaningful. In this context, conduction block at baseline was more frequent in older participants (8/35 vs. 3/34 for more youthful participants). Fifth, the findings may be spurious, possibly attributable to chance. Additional efficacy studies Rafoxanide with opicinumab are needed to shed light on the effect of baseline age on response to therapeutic remyelination. The lack of statistically significant conversation between the main endpoint and treatment windows or timing of steroid administration at week 24 may be attributed to Rafoxanide the small sample size, as the RENEW study was powered only for an 80% treatment effect with one\tail alpha of 0.1 for the primary endpoint. Notwithstanding, there appears to be a consistent numerical trend suggesting greater improvement in patients treated sooner ( 25?days from onset of AON) with opicinumab ( em P? /em = em ? /em 0.12, vs. placebo) and in patients randomized to opicinumab and treated sooner with high\dose methylprednisolone ( 15?days from onset of AON; em P? /em = em ? /em 0.14, vs. placebo). The axonal protective potential of opicinumab, if given soon after onset of CNS inflammatory demyelinating injury, should Jag1 be evaluated in additional studies aiming to initiate treatment sooner that this 28\day window in this study. Results from a single\center academic study with phenytoin that enrolled within 14?days of AON onset suggest that treatment Rafoxanide with candidate RGCL protective brokers could be initiated earlier after onset of AON symptoms.23 The apparent lack of influence of visual impairment and brain MRI data in stratifying patients according to VEP latency prolongation at week 24 is noteworthy. However, the subgroup analyses showed a pattern for a treatment benefit in participants with more impaired pretreatment HCVA ( em P? /em = em ? /em 0.08). This could indicate that opicinumab\mediated repair via remyelination may be more effective and relevant in participants with greater pre\treatment HCVA impairment, barring severe injury to the optic nerve including the ganglion cell neurons in the retina. In this study, the conversation between VEP latency and brain T2 lesion volume is hard to interpret due to the small sample.