Exogenous Cell Myelin Repair and Neuroprotection in Multiple Sclerosis

Abstract

The loss of myelin has serious functional consequences in multiple sclerosis (MS) and other demyelinating disorders and may place demyelinated axons at risk of subsequent degeneration. Hence, remyelination has two major consequences: it will restore and speed impulse conduction (Smith et al. 1979) and it may protect axons against degeneration, thus acting as a form of neuroprotection (Irvine and Blakemore 2008; Kornek et al. 2000). The current available treatments of MS do not promote remyelination as far as is known; hence there is a critical need for such a restorative therapy. It is well known that in experimental demyelinating disease, the CNS has remarkable ability to be remyelinated by an endogenous response (Blakemore 1973; Franklin and Ffrench-Constant 2008; Ludwin 1978), and recently, it was clearly demonstrated that widespread endogenous remyelination can lead to restoration of function (Duncan et al. 2009). Likewise in MS, extensive remyelination occurs early in the disease (Kornek et al. 2000; Prineas and Connell 1979; Raine and Wu 1993) and can also be seen at later stages (Patani et al. 2007; Patrikios et al. 2006) although it is not clear how long the human CNS can sustain an endogenous response. However it is likely that the aging CNS remyelinates less efficiently (Goldschmidt et al. 2009; Shen et al. 2008; Shields et al. 1999). In later stages of the disease, endogenous remyelination will only occur if the remaining cells of the oligodendrocyte lineage, either progenitors or mature cells, in or very close to lesions, can be mobilized and differentiate into myelinating oligodendrocytes. As there are no proven strategies available that will promote such a response in the human CNS, the transplantation of cells into focal areas of demyelination or multiple sites using a more disseminated delivery approach may be important therapeutically.