Neuroprotective therapies for multiple sclerosis and other demyelinating diseases

Abstract

Damage to the Central Nervous Systems (CNS) in Multiple Sclerosis (MS) seems to be mainly due to chronic inflammation of the CNS with superimposed bouts of inflammatory activity by the adaptive immune system. The immune mediated damage can be amplified by neurodegenerative mechanisms in damaged axons including anterograde or retrograde axonal or transynaptic degeneration, synaptic pruning and neuronal or oligodendrocyte death. As such, it is highly unlikely that CNS damage can be prevented using only immunomodulatory drugs. For this reason, neuroprotection, aimed at preventing axonal, neuronal, myelin, and oligodendrocyte damage and cell death in the presence of this toxic microenvironment is highly pursued in MS and other demyelinating diseases. Neuroprotective strategies target different processes including oxidative stress, ionic imbalance (sodium, potassium or calcium), energy depletion, trophic factor support, metabolites balance, excitotoxicity, apoptosis, remyelination, etc. Although none of these strategies have translated into approved drugs to date, improvement in the understanding of underlying biology, in the design of clinical trials specific for assessing neuroprotection, and new technologies for developing novel therapies for neuroprotection suggest a new avenue for treating MS, Optic Neuritis or Neuromyelitis Optica (NMO). Several of these therapies are now entering clinical phases and if successful, such strategies would improve patients’ quality of life, and will be even more critical for patients with progressive MS. In the event that such therapies target natural repair mechanisms rather than disease specific processes, they can potentially be useful for other brain diseases such as stroke, neurodegenerative diseases, brain trauma or epilepsy.