Multiple sclerosis tissue proteomics

Dr Michael Barnett, Professor John Prineas and Dr Ben Crussett continue their research at Sydney University, with anticipated positive outcomes.

While the cause of MS is unknown, an immune response to a self or foreign protein (antigen) is likely to play an important role. This project uses new laboratory techniques to discover and characterise potential antigens and other molecules important to the cause of MS. The identification of these proteins may lead to targeted, more effective treatments for MS.

Unlike other studies, this involves the application of new technologies to tissue from an unparalleled brain and spinal cord bank comprising greater than 300 MS cases, over 30 with disease duration of less than 3 months. The identification of an MS-specific antigen within microglial nodules in periplaque normal-appearing white matter, or of new molecular targets in pre-phagocytic tissue integral to lesion formation/expansion, may help to unravel the pathogenesis of the disease and ultimately lead to the development of novel, targeted therapies.

This project is addressing these issues by applying emerging technologies to an existing and unique bank of acute and chronic MS tissue. By utilising a combination of laser capture microdissection, advanced proteomics and immunofluorescence microscopy, we seek to establish molecular profiles that are specific to the earliest phases of tissue alteration in MS, namely the pre-phagocytic white matter lesions that characterise early disease, and the periplaque white matter surrounding expanding acute and chronic lesions that contain biomarkers of an MS-specific immune response previously identified by our group.

This work should significantly advance our understanding of the pathogenesis of events leading to the formation of classical active MS plaques and, potentially, to aid directly in the development of more effective, targeted therapies.