An In Silico Target Specific Drug Repurposing Approach for Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a multifocal demyelinating disease with progressive neurodegeneration caused by an increased auto immune response to self-antigens. Based on the ability of remyelination, MS is characterized into 4 subtypes: Relapsing Remitting MS (RRMS) (most commonly found ∼87%), Primary Progressive MS (PPMS), Secondary Progressive MS (SPMS), and Progressive Relapsing MS (PRMS). MS is termed as T cell-mediated autoimmune disorder with a predominant expression of CD8+ cells, (involved (MHC-I) activation), CD4+ T cells and microglia/macrophages. The pathophysiology of MS involves focal demyelination (myelin sheath destruction), oligodendrocyte destruction and astrocyte proliferation. Majority of people experience symptoms like muscle spasms, constipation, weakness, urinary problems and alterative sessions of relapses and remissions between the ages of 20 and 40. Currently, Disease Modifying Therapies (DMTs) were known to decrease the frequency and severity of relapses, exacerbations and development of new lesions. To date, U.S FDA approved drug for the treatment of PPMS is Ocrelizumab. Nevertheless, many drugs exhibited success in the preclinical phases and successfully reached clinical trials.