Clinical response to Nabiximols correlates with the down-regulation of immune pathways in Multiple Sclerosis.

BACKGROUND:

Nabiximols (Sativex^® ) is a cannabinoid-based compound used for the treatment of moderate to severe spasticity in multiple sclerosis (MS). The aim of the study is to investigate the effect of the administration of Nabiximols on blood transcriptome profile of MS patients and to interpret it in the context of pathways and networks.

METHODS:

Whole-genome expression profiling was performed in whole blood of 33 MS subjects at baseline (B) and after 4 weeks (4W) of drug treatment. Patients were classified in responders (n=19) and non-responders (n=14). Pathway and network analyses on genes modulated by the drug were performed, followed by in vitro stimulations of peripheral blood mononuclear cells (PBMCs) with pro-inflammatory agents, to support the immunomodulatory properties of the drug.

RESULTS:

Individual effect size was modest, however, we observed a downregulation of several immune-related pathways after 4 weeks of treatment which was more pronounced when restricting analyses to responders. Interesting hub molecules functionally related to the immune system emerged from network analysis, including NFKB1, FYN, MAP14 and TP53. The immunomodulatory properties of the drug were confirmed through in vitro assays in PBMCs collected from MS patients.

CONCLUSIONS:

Our findings support the immunomodulatory activity of cannabinoids in MS patients. Further studies in more specific cell types are needed to refine these results. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.