Abstract: 260
Type: Oral
Does the white matter lesion in multiple sclerosis (MS) still matter in the age of highly effective disease-modifying therapy, which acts primarily to stop new lesions from forming? Evidence suggests that it does - not just because the most effective therapies are also the riskiest, but also because therapies that stop new lesions from forming do not appear to impact chronic inflammation or enhance repair. In this brief talk, I will discuss our lab's recent findings about the development and early repair of lesions in the brain and spinal cord in MS, and how those findings are mirrored in inflammatory demyelinating lesions in a primate model of MS. I will describe pathological changes that occur prior to demyelination and show how failed early repair can lead to smoldering inflammation at the lesion edge, with its attendant slow myelin destruction. Finally, I will speculate about how magnetic resonance imaging (MRI) can be used to distinguish among long-term lesion outcomes (chronic inflammation, remyelination, and quiescent demyelination), opening the possibility of surrogate outcomes for trials of neuroprotection and regeneration.
Disclosure: Daniel S. Reich is supported by the Intramural Research Program of NINDS/NIH (USA) and has received support for collaborative research projects from the Myelin Repair Foundation and Vertex Pharmaceuticals.
Abstract: 260
Type: Oral
Does the white matter lesion in multiple sclerosis (MS) still matter in the age of highly effective disease-modifying therapy, which acts primarily to stop new lesions from forming? Evidence suggests that it does - not just because the most effective therapies are also the riskiest, but also because therapies that stop new lesions from forming do not appear to impact chronic inflammation or enhance repair. In this brief talk, I will discuss our lab's recent findings about the development and early repair of lesions in the brain and spinal cord in MS, and how those findings are mirrored in inflammatory demyelinating lesions in a primate model of MS. I will describe pathological changes that occur prior to demyelination and show how failed early repair can lead to smoldering inflammation at the lesion edge, with its attendant slow myelin destruction. Finally, I will speculate about how magnetic resonance imaging (MRI) can be used to distinguish among long-term lesion outcomes (chronic inflammation, remyelination, and quiescent demyelination), opening the possibility of surrogate outcomes for trials of neuroprotection and regeneration.
Disclosure: Daniel S. Reich is supported by the Intramural Research Program of NINDS/NIH (USA) and has received support for collaborative research projects from the Myelin Repair Foundation and Vertex Pharmaceuticals.