Advancement of therapies for neuroprotection in multiple sclerosis.
There is increased awareness and interest in the neurodegenerative component of multiple sclerosis. Available disease-modifying agents, primarily developed to suppress inflammation and modulate the immune system, have not been effective at halting neurodegeneration. Although understanding of the inter-relationship between the autoimmune and neurodegenerative processes continues to evolve, at a minimum, both elements are present in the disease. Accordingly, a more balanced treatment strategy should be directed at both processes, and it is necessary to introduce agents with prominent neuroprotective properties to augment immunomodulatory therapies. Potential agents reviewed include sodium channel-blocking drugs, glutamate antagonists, hormones, tetracyclines, polyphenolic compounds, cannabinoids and serotonin reuptake inhibitors. As putative neuroprotective agents are being investigated, it is being recognized that most agents are not exclusively neuroprotective or immunomodulatory, and mechanisms of action can inhibit toxic pathways or activate trophic pathways. Critical to establishing new agents is the concomitant development of outcomes specific to neuroprotective change. Human studies have been initiated to test the most promising agents for feasibility, safety and efficacy.
Lo
Albert
A
Department of Clinical Neurosciences, Brown University, Providence, RI, USA.