Strategy For Treatment Of Multiple Sclerosis Research Articles

Neuroprotection in multiple sclerosis

In chronic inflammatory diseases like multiple sclerosis (MS), neuroprotection refers to strategies aimed at prevention of the irreversible damage of various neuronal and glial cell populations, and promoting regeneration. It is increasingly recognized that MS progression, in addition to demyelination, leads to substantial irreversible damage to, and loss of neurons, resulting in brain atrophy and cumulative disability. One of the most promising neuroprotective strategies involves the use of bone marrow derived stem cells. Both hematopoietic and non-hematopoietic (stromal) cells can, under certain circumstances, differentiate into cells of various neuronal and glial lineages. Neuronal stem cells have also been reported to suppress EAE by exerting direct in situ immunomodulating effects, in addition to their ability to provide a potential source for remyelination and neuroregeneration. Preliminary results from our laboratory indicate that intravenous or intracerebral/intraventricular injection of bone marrow derived stromal cells could differentiate in neuronal/glial cells and suppress the clinical signs of chronic EAE. Both bone marrow and neuronal stem cells may therefore have a therapeutic potential in MS. It seems that future treatment strategies for MS should combine immunomodulation with neuroprotective modalities to achieve maximal clinical benefit.

Intranasal administration of interferon beta bypasses the blood–brain barrier to target the central nervous system and cervical lymph nodes: a non-invasive treatment strategy for multiple sclerosis

Intranasal (IN) administration of IFNβ-1b was examined as a route for targeted delivery to the rat central nervous system (CNS). Intranasal administration resulted in significant delivery throughout the CNS and cervical lymph nodes with low delivery to peripheral organs. At similar blood levels, intravenous (IV) administration of IFNβ-1b yielded 88–98% lower CNS levels and 100–1650% greater peripheral organ levels compared to intranasal. Autoradiography confirmed much greater delivery to the CNS with intranasal administration. Intranasally administered IFNβ-1b reached the brain intact and produced tyrosine phosphorylation of IFN receptor in the CNS. Intranasal administration offers a non-invasive method of drug delivery for multiple sclerosis (MS) that bypasses the blood–brain barrier (BBB) and directly targets the CNS and lymph nodes.

Approaches to the treatment of central nervous system autoimmune disease using specific neuroantigen.

The ultimate aim in the treatment of autoimmune disease is to restore self-tolerance to the autoantigen(s) in question. In lieu of this ideal result, the conversion of a destructive or pathogenic autoimmune response into one of benign autoimmunity would also be highly desirable. In either case the use of the antigenic epitope, which is the target of the destructive immune response, would ideally be employed so as to give specificity to the protection without the need for long-term immunosuppression. This review describes a number of different approaches using various forms, doses, and routes of injection of specific neuroantigen to inhibit the different clinical varieties of autoimmune encephalomyelitis in a number of animal models; all done with the view to translating the findings into the clinic for the treatment of multiple sclerosis. We conclude that any treatment strategy for multiple sclerosis (MS) must have a number of features: it must be clinically acceptable, specific, long-lasting, require only short-term treatment, able to shunt off ongoing disease, and have the potential to prevent or deal with epitope spreading. Few of the approaches we describe fulfill all of these criteria. We suggest that investigations of new adjunctive agents to be used with a specific antigen be pursued, and that currently the use of chimeric proteins or DNA vaccination with or without the new adjunctives may hold the most hope for the future.