Special BMI Seminar // Neurodegeneration in multiple sclerosis: what have we learned from pathology?

Multiple Sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS), initially characterised by acute relapses of neurological dysfunction followed by remission. After a variable period this is followed in the majority of patients by a slow and irreversible progression of neurological dysfunction. Although the acute clinical deficits during early MS can increasingly be prevented with drugs that target the acute influx of peripheral immune cells, there are at present no licensed therapeutic agents available that significantly slow the rate of clinical progression. The pathology at this advanced stage is characterized by the accumulation of chronic demyelinated lesions and axonal loss in the white matter and extensive cortical grey matter pathology. Actually, tissue damage in the grey matter is a unique and key component of MS and provides the best correlate of the rate of progression. Thus, it is becoming generally accepted that neurodegeneration plays a key role in the progressive stage of the disease and drives clinical disease progression. In my talk I will first address key pathological hallmarks of early and advanced MS and in the second part focus on how mitochondrial dysfunction drives neurodegeneration in MS disease progression.