Is it clinically relevant to repair focal multiple sclerosis lesions?

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, predominantly, but not exclusively, involving the normal appearing white matter. Until very recently we believed that nervous dysfunction in MS was completely depending on the accumulation of lesions in the white matter of the CNS. As a consequence, lesions seen by magnetic resonance imaging (MRI) have been considered a potential surrogate end point in clinical trials assessing new MS treatments. More recently, this concept have been challenged by the emerging evidences, mostly from pathological and MRI studies, that lesions may be located also in grey matter and that the white and grey matter not affected by lesions is abnormal. The causes of this normal appearing grey and white matter damage are still debated and there is the possibility that such a damage is largely independent from the lesions. There are accumulating evidences that the pathogenetic mechanisms in MS may differ in the early and in the late phases of the disease. Early MS is associated with recruitment of systemically derived immune cell populations and inflammatory lesions. Late MS results characterised by a predominantly compartimentalised immunological response. These recent modifications on our views of the MS pathogenesis and pathophysiology do have major implications on the therapeutic strategies, including the use of treatments aiming to enhance the recovery, such as stem cell therapy.