Neuroprotection in multiple sclerosis: a therapeutic challenge for the next decade.
Multiple sclerosis (MS) is the commonest cause of progressive neurological disability amongst young, Caucasian adults. MS is considered to be an auto-immune disease that results from an attack against myelin, the layer which surrounds axons. The pathophysiology of MS is complex, with both demyelination and axonal degeneration contributing to what is essentially an inflammatory neurodegenerative disease. Axonal loss is increasingly being accepted as the histopathological correlate of neurological disability. Currently, the underpinnings of neurodegeneration in MS, and how to promote neuroprotection are only partly understood. No established treatments that directly reduce nervous system damage or enhance its repair are currently available. Moreover, the ability of currently available immunomodulatory therapies used to treat MS, such as interferon-beta, to prevent long-term disability is uncertain. Results from short-term randomized-controlled trials suggest a partial benefit with regards to disability outcomes, but this is yet to be established in long-term studies. Novel neuroprotective agents have been identified in preclinical studies but their development is being hampered by the absence of appropriate clinical platforms to test them. In this article, we will discuss some of the principal therapeutic candidates that could provide neuroprotection in MS and emerging methodologies by which to test them.
Van der Walt
Anneke
A
The Royal Melbourne Hospital, Grattan St. Parkville, Melbourne, Australia; Centre for Neuroscience, University of Melbourne, Australia. Anneke.vanderwalt@mh.org.au
Butzkueven
Helmut
H
Kolbe
Scott
S
Marriott
Mark
M
Alexandrou
Estella
E
Gresle
Melissa
M
Egan
Gary
G
Kilpatrick
Trevor
T
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D002986:Clinical Trials as Topic / Q000379:methods; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*
D018696:Neuroprotective Agents