Objectives: To investigate if MS subjects treated with PRF 10mg BID will show a greater benefit from active enabled motor training compared with placebo. Methods: Single center, phase 4, pilot, placebo-controlled, double-blind 18 weeks study. Fifteen patients were randomized to receive PRF 10 mg BID and fifteen to received placebo BID. All patients participated in active enabled motor training of 3 sessions of 1 hour/week for 6 weeks. Patients were evaluated at -4, 0, 6 and 14 weeks using the timed 8 meters walk (8 MW), the 6 minute walk (6 MW) and the timed sit to stand (STS). Results: The PRF treated group achieved a higher mean percent improvement from baseline in all tasks at both 6 and 14 week time points. The difference reached statistical significance (mean difference of 14.29, p=0.046) for the 8MW at the 14 week time point. A higher incidence of responders (>20% improvement from baseline) was seen in the PRF treated group at 6 weeks on the 8MW (odds ratio [OR] of 2.31) and the 6MW (OR of 1.63), and at 14 weeks on the 8MW and the STS (OR of 2.0). Conclusions: PRF in MS patients appears to enhance the benefit of active enabled motor training and to better sustain it over the following 8 weeks.

Background: Motor evoked potentials (MEP’S) measure myelin/axonal integrity of the central nervous system. MEP’s reliability and correlation to conventional clinical measures in multiple sclerosis (MS) patients have yet to be demonstrated. Alemtuzumab is a high efficacy therapy used in patients with MS. Its longitudinal impact on electrophysiological measures has yet to be examined. Methods: This is a single center, observational study. 10 patients with MS who received their first cycle of alemtuzumab within less than 3 months were evaluated with both clinical and MEP’s measures at baseline and every 6 months thereafter for 36 months. MEP’s were repeated two weeks after every time point. We report our preliminary analyses. Results: Patient follow-up ranges from 6 to 36 months. The intraclass correlation coefficient (ICC) between two consecutive time points were good with values of 0.774 for the biceps and 0.867 for the tibialis anterior with p values less than 0.0005 for both. The correlation for the biceps MEP’s to the 9 hole peg test (9HPT) was 0.51 with p less than 0.0005 and for the tibialis anterior MEP’s to the 6 minute walk test (6MWT) was -0.411 with p=0.01. Conclusions: Our preliminary analyses demonstrate that MEP results are reproducible and correlate with clinical measures.

Background: Glioblastoma Multiforme (GBM) has well documented systemic and local immunosuppressive mechanisms to escape immune surveillance and grow. GBM tumor cells as well as the microglia within it have a high incidence of PD-L1 surface expression which makes it more susceptible to anti-PD-L1 antagonism and ADCC through avelumab therapy. Methods: This is a single center, phase 2, open label, add-on, single dose study of 156 weeks duration in patients receiving standard therapy for newly diagnosed GBM. In total 30 patients will be entered into the study within 3 weeks of finishing their last day of combined radiotherapy/temozolomide. The following are the results of the first interim analysis completed when the first eight patients completed 52 weeks or an end of study visit. Results: 24 patients have so far started therapy. There as been no unexpected treatment emergent adverse event (TEAE). Two patients transiently withheld therapy because of immune related TEAE’s and none permanently. The objective response rate at week 52 for the first eight patients was 50% with 2 (25%) having a complete response and 1 (12.5%) a partial response. Conclusions: These preliminary results suggest that the addition of avelumab to standard therapy in patients with GBM is safe. Efficacy trends look promising.

Objectives: The objectives of this study are to understand the impact of natalizumab on cognition beyond two years of therapy and to investigate whether baseline characteristics are predictive of clinical response. Methods: This is a single-center, 24-month, observational study. Sixty-three patients treated with natalizumab were assessed prior to monthly infusions using a Cogstate battery and the SDMT. A linear mixed model was conducted with duration of natalizumab therapy as a between-subjects factor (<=2 or >2 years), assessment as a within-subjects factor, and MSSS as a covariate. Results: There were no statistically significant differences between the key demographic variables aside for the MSSS (p=.0074). No patient showed evidence of sustained cognitive deterioration over the 24 month period. Irrespective of time on natalizumab, significant improvements were observed at the group level in executive function, verbal memory and working memory, whereas processing speed and attention remained unchanged. Impaired cognition or any other baseline parameter did not influence the trajectory of cognitive change over 24 months. Conclusion: Our results suggest that natalizumab preserves cognitive function, including the ability to learn, for 4 years and beyond of continuous therapy. This occurs irrespective of baseline characteristics.