Laura Gianni

University of Melbourne

Project

Identify protein markers of disease in MS

Co-Investigators

Supervisor: Dr Anthony Purcell, University of Melbourne

Funding

$78,000 over 2009 - 2010 from the MS Angels

Project Summary

Biomarkers are biological substances (e.g. proteins) that can be used for diagnosis, measuring disease progression or the effects of treatment. I will examine levels of protein expression in animal models and diseased human brain tissue to help clarify unresolved issues in MS. In doing so, it is hoped that disease biomarkers originally identified in the animal model will be applicable to patients with MS. Biomarkers will play a vital role in future clinical practice as they may very well represent novel targets for therapy or aid in earlier and more effective MS diagnosis.

MS is a primary example of a complex disease that can benefit from the elucidation of disease biomarkers by the application of novel unbiased discovery tools such as proteomics. Currently there is a lack of biomarkers available to ascertain the early and accurate diagnosis of the disease, as well as a major inadequacy in terms of effective therapeutic interventions.

Advances in proteomics have allowed us to embark on the discovery-driven phase of biomedical research which offers the opportunity to accelerate the search for biomarkers that may provide insight into molecular mechanisms underlying MS pathogenesis. Elucidating the profile of differentially expressed proteins in both an animal model of MS and human MS tissue will allow for the identification of candidate biomarkers for MS.

Moreover, these biomarkers will facilitate the development of novel therapeutic compounds, aid the early elimination of unpromising drugs (Phase I/II trials) and allow the identification of surrogate endpoints for monitoring longterm therapeutic efficacy. The knowledge acquired from proteomics will allow researchers to make efficient comparisons across several array platforms such as high-density SNP mapping and metabolomics

It has recently come to light that the cerebellum and the brainstem of murine subjects with MS have increased susceptibility to cellular infiltration and blood brain barrier (BBB) disruption. In fact, these regional differences in CNS vasculature are thought to modulate inflammatory infiltration across the BBB and may be related to the clinical disease profile (Personal communication, Dr. Jacqueline Orian). However, to date there have been limited proteomic investigations into the molecular mechanisms leading to BBB breakdown and the associated neurological deficits.

New initiatives aimed at deciphering the proteome of the CNS between control and diseased states are thus required. This study will be the first of its kind applied to brain tissue involving 2D-DIGE coupled to Mass Spectrometry, a contemporary method for deducing qualitative as well as quantitative information about relative levels of protein expression. Clinical proteomics, the application of proteomics in the field of medicine, has the potential to revolutionise the field of clinical practice by providing a unique set of tools for defining disease states and improving individual tailoring of treatment.