title: Neuroprotection in multiple sclerosis: therapeutic strategies and clinical trial design.
abstract: OBJECTIVE
  Degeneration of axons and their cell bodies is thought to occur progressively from the onset of multiple sclerosis and to be a significant cause of increasing disability. The mechanisms of neurodegeneration are becoming clearer and this work has already indicated potential molecular targets for therapeutic intervention to prevent neuronal injury. Attention is being directed at the appropriate design of clinical trials to test neuroprotection as a major strategy for the management of multiple sclerosis. The subtype of multiple sclerosis, the primary outcome measure and other detailed design issues remain controversial. This review considers the rationale for different therapeutic strategies for neuroprotection and discusses the controversies of trial design.
  
  
  RESULTS
  The experimental work on neuroprotection in animal models of inflammatory axonal degeneration and consideration of outcome measurement in multiple sclerosis have developed sufficiently to enable trials of neuroprotection to be planned, powered and implemented. Trials assessing neuroprotection with tetrahydrocannabinol and lamotrigine are imminent; both will involve subjects with progressive forms of multiple sclerosis.
  
  
  CONCLUSIONS
  These advances mean that neuroprotection is emerging as a potentially important strategy for preventing disability in multiple sclerosis. It is likely that a range of neuroprotective strategies will be tested alone and in combination in future trials, and that trial design will be refined as experience accumulates.
authors.affiliation: National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. r.kapoor@ion.ucl.ac.uk
authors.forename: Raju
authors.initials: R
authors.lastname: Kapoor
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D018696:Neuroprotective Agents