Project 2022-042: Spatial Temporal Dissection of Inflammation and Orchestrated Brain-Immune Tissue Interactions in Multiple Sclerosis

  • Therapeutic Area: Immunology & Inflammation; Neurology/Pain/Sleep Disorders; Rare & Genetic Diseases
  • Technology Platform: Other
  • Development Stage: Concept (Early Opportunities)

Abstract

Multiple Sclerosis (MS) is a prevalent primary demyelinating disease of the central nervous system(CNS), affecting millions of individuals worldwide. Recent epidemiological and molecular evidence strongly implicates the Epstein-Barr Virus (EBV), and molecular mimicry as the causal agent for MS. EBV vaccines currently undergoing various stages of clinical trials have the potential to prevent MS. However, they do not have a direct therapeutic role in managing patients who currently live with MS, nor allow prediction and intervention regarding the progression of inflammation and demyelination leading to MS. Treatment of MS will require detailed temporal-aligned snapshots to uncover molecular tissue events over the disease course. We propose to leverage a clinical cohort of tissue biopsies from active demyelinating lesions in MS patients. This cohort encompasses patients with biopsy-proven active MS lesions and a diagnosis of MS on clinical follow-up. In addition, BIDMC Neuropathology also has archival autopsy brain tissue with late stage MS lesions. Combining these archival tissue samples with spatial-omics platforms available at BIDMC and our laboratories will allow a unique opportunity to interrogate molecular inflammatory pathways and assess the roles of CNS and immune cell types during MS disease initiation and progression. Successful completion of the proposed work, in addition to novel systems-level insights into MS disease, will be vital for the identification of new interventions and therapeutic targets with the potential for intellectual property for BIDMC. The deep-phenotyping nature of this study will also be critical for future externally sponsored research into this emerging area using spatially-resolved technologies.

Contact Information

Name: Stan Mah

Email: smah@bidmc.harvard.edu

Phone: 617-667-0573