An open label study of a novel immunosuppression intervention for the treatment of amyotrophic lateral sclerosis.

Neuroinflammation is increasingly tied to disease progression in amyotrophic lateral sclerosis (ALS). Participants in the first-in-human trial of intra-spinal allogeneic stem cell therapy for ALS received immunosuppression, and one participant saw dramatic improvement across multiple outcome measures. The primary objective of this study (NCT01884571) was to assess the rate of clinical response to the same immunosuppressive regimen using basiliximab, tacrolimus, mycophenolate, and prednisone in people with ALS. A clinical response was defined as an improvement on the revised ALS Functional Rating Scale (ALSFRS-R) by six points over a 6-month period. Thirty-one participants were enrolled in this 15-month open label study and received an identical immunosuppression regimen. Clinical outcome measures and biospecimens were collected before, during, and after the treatment regimen. No patients met the pre-defined responder criteria. No difference in mean ALSFRS-R slope was seen in the treatment period compared to the pretreatment period (p = 0.200). The regimen was generally safe in an ALS population, although only 18 out of 31 patients completed the full 6 months of immunosuppression. Analyses of immune markers showed no change in peripheral regulatory T-cell populations during treatment compared to pretreatment (p = 0.200). Analysis of cerebrospinal fluid (CSF) cytokine levels showed an increase in IL-2 levels with immunosuppression (p = 0.004) followed by decrease during post-treatment follow-up (p = 0.031). Further studies are needed to understand how manipulation of the immune system may affect disease progression in ALS.