Therapeutic approaches to multiple sclerosis: an update on failed, interrupted, or inconclusive trials of neuroprotective and alternative treatment strategies.

Currently approved multiple sclerosis (MS) therapeutics have a mainly anti-inflammatory mode of action. However, a number of promising clinical trials have been initiated that either focus on neuroprotection or follow completely different treatment strategies. So far, all of these clinical trials have failed to show efficacy or had to be halted prematurely because of unexpected adverse events.

Therapeutic approaches to multiple sclerosis: an update on failed, interrupted, or inconclusive trials of immunomodulatory treatment strategies.

Multiple sclerosis (MS) continues to be a therapeutic challenge, and much effort is being made to develop new and more effective immune therapies. Particularly in the past decade, neuroimmunologic research has delivered new and highly effective therapeutic options, as seen in the growing number of immunotherapeutic agents and biologics in development. However, numerous promising clinical trials have failed to show efficacy or have had to be halted prematurely because of unexpected adverse events.

Altered expression of ion channel isoforms at the node of Ranvier in P0-deficient myelin mutants.

To elucidate the impact of myelinating Schwann cells on the molecular architecture of the node of Ranvier, we investigated the nodal expression of voltage-gated sodium channel (VGSC) isoforms and the localization of paranodal and juxtaparanodal membrane proteins in a severely affected Schwann cell mutant, the mouse deficient in myelin protein zero (P0). The abnormal myelin formation and compaction was associated with immature nodal cluster types of VGSC. Most strikingly, P0-deficient motor nerves displayed an ectopic nodal expression of the Na(v)1.