The challenge of multiple sclerosis: How do we cure a chronic heterogeneous disease?

Abstract

Multiple sclerosis is (MS) a T-cell autoimmune disease characterized by a relapsing-remitting followed by a progressive phase. Relapses are driven by the adaptive immune system and involve waves of T helper cell 1 (Th1), Th17, and CD8 cells that infiltrate the nervous system and provoke a attack. These cells are modulated by regulatory T and B cells. Infiltration of T cells into the nervous system initiates a complex immunological cascade consisting of epitope spreading, which triggers new attacks, and activation of the innate immune system (microglia, dendritic cells, astrocytes, B cells), which leads to chronic inflammation. The secondary progressive phase is due to neurodegeneration triggered by inflammation and is driven by the innate immune system. Why a shift to the progressive stage occurs and how to prevent it is a central question in MS. Effective treatment of MS must affect multiple disease pathways: suppression of proinflammatory T cells, induction of regulatory T cells, altering traffic of cells into the nervous system, protecting axons and myelin, and controlling innate immune responses. Without biomarkers, the clinical and pathological heterogeneity of MS makes treatment difficult. Treatment is further hampered by untoward adverse effects caused by immune suppression. Nonetheless, major progress has been made in the understanding and treatment of MS. There are three definitions of cure as it applies to MS: (1) halt progression of disease, (2) reverse neurological deficits, and (3) prevent MS. Although the pathways to each of these cures are linked, each requires a unique strategy.

Replication of top markers of a genome-wide association study in multiple sclerosis in Spain

“…An additional possibility is that what appears to be a homogeneous MS phenotype might, in fact, be due to distinct etiologies in different MS patients in such a way that a genuine effect pertinent to a specific category of patients could pass undetected when analyzing the whole collection. 27 Finally, the question of population-specific MS risk genes is as yet unanswered. Given the lower prevalence of MS in the Mediterranean areas including Spain (prevalence of 0.0008, http://www.mult-sclerosis.org/prev_tab.html), it remains to be seen whether the same gene-environment interactions or genetic penetrance have a role in MS irrespective of geographic/ethnical background.…”

Neurofilament light chain serum levels correlate with 10‐year MRI outcomes in multiple sclerosis

“…Multiple sclerosis (MS) is a demyelinating and degenerative disease with a heterogeneous disease course 1. Patients experience periodic relapses and varying ranges of disability accrual over their lifetime.…”

Improving Multiple Sclerosis Plaque Detection Using a Semiautomated Assistive Approach

“…[2][3][4][5][6] Recent advances in imaging, including 3T 3D volumetric T2 FLAIR sequences, allow better resolution of small demyelinating lesions, resulting in better clinicoradiologic correlation. 7,8 Despite advances in imaging techniques, conventional side-by-side comparison (CSSC) is often subject to a reader's expertise.…”