A new view of MS progression: Implications for drug development
This presentation highlights mechanisms of multiple sclerosis (MS) worsening. A key point is to recast the clinical descriptors of MS disease state. Rather than retaining categorical descriptors, we propose mechanistic phenotypic terminology: ‘relapsing-pathology-dominant’ and ‘progressive-pathology-dominant’. We focus in particular on Progression Independent of Relapse Activity (PIRA) which begins during the RPD phase and becomes more evident as patients age during the PPD phase. Mechanisms for PIRA include chronic-active demyelinating lesions (CALs) and subpial cortical demyelination, as well as nerve fiber injury. We propose that much but not all of this tissue injury is driven by autonomous meningeal lymphoid aggregates, present before disease onset and unresponsive to current therapeutics. Importantly, the adaptive immune process represented by meningeal aggregate signaling to parenchymal infiltrated leukocytes and microglia may well be susceptible to treatment by advanced CNS active immune therapeutic initiatives. Conventional magnetic resonance imaging (MRI) and animal models have been ineffective for understanding pathological processes which produce PIRA. Recently, specialized MRI has been used to detect CALs as paramagnetic rim lesions (PRLs). This MRI technology enables novel radiographic-neuropathologic-biomarker/clinical correlations and holds promise for clinical development aimed to treat PIRA and PPD aspects of MS.
About the speaker
Throughout his career, Dr Richard Ransohoff has balanced patient care with groundbreaking research on inflammation in neurological diseases, particularly multiple sclerosis. He is a co-founder of Abata Therapeutics, where he served as interim chief medical officer. He now spearheads neurological and immunological company creation as a Venture Partner at Third Rock Ventures.
Previously, at Cleveland Clinic, he founded the Neuroinflammation Research Center and led a team in neuroinflammatory target discovery at Biogen. Renowned for MS care, he’s received awards like the John J. Dystel Award for MS Research.
