Multiple Sclerosis: New Insights in Pathogenesis and Novel Therapeutics

Abstract

Concepts of multiple sclerosis (MS) have shifted from the traditional view of a T cell-mediated, demyelinating disease of the white matter to include a broad range of immunopathogenic mechanisms, axonal damage, and widespread gray matter pathology. The cause of MS remains unknown, but recent epidemiological work has focused on genetic factors; environmental factors such as vitamin D, sunlight, and Epstein-Barr virus; and the controversial theory of chronic cerebrospinal venous insufficiency. Revised criteria facilitate making the diagnosis of MS. Emerging therapies are rapidly expanding treatment options, including both parenterally administered and oral medications. Strategies to preserve tissue, promote repair, and restore function are under development, and it is anticipated that they will provide better options for patients with progressive disease.

Insights into the Role of Neuroinflammation in the Pathogenesis of Multiple Sclerosis

“…These studies attributed the findings to the level of exposure to sun light and vitamin D intake through diet, demonstrating a clear association between vitamin D-deficiency and risk of MS development [15,[23][24][25]. Many of these studies suggested that lower serum vitamin D levels could be predictive of higher incidence of relapses among MS patients [11,[26][27][28].…”

Neurological disorders and therapeutics targeted to surmount the blood–brain barrier

“…85,169 In particular, a specific subset of T helper cells (Th-17) has been identified to be the leading cause of multiple sclerosis, because they secrete interleukin-17 and are endowed with an ability to open the blood-brain barrier, thereby driving the neuronal insult. 86 In addition, the immune attack towards myelin is boosted by recruitment of T cells from the periphery and activation of antibody-secreting B cells by reactive T cells, culminating in an assault on myelin, followed by demyelination. 87,88 Based on severity of symptoms, multiple sclerosis is classified into four subtypes.…”

Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis: The Hydrostatic-Immune Paradigm and the Flow Cytometry as a Diagnostic Tool

“…In the initial stages of the disease, before lymphoid neogenesis occurs and tertiary lymphoid structures within the meningeal compartment are able to sustain a continuous inflammatory process [69], these interactions probably take place in CLNs [3] and are dependent on CNS antigen transport to those sites [57]. So, CLNs may act as loci of antigen presentation and T-or B-lymphocyte priming [54] but also as sites of tolerance induction towards CNS antigens [70,71].…”

“…Both genetic and environmental factors have been implicated in the pathogenesis [2]. The precise cause remains largely unknown, but there is evidence of a myelin-antigen-specific, Th1-mediated immune process resulting in macrophage-mediated demyelination, axonal loss and gliosis [3].…”