Restricted Research - Award List, Note/Discussion Page

Fiscal Year: 2014

2082  The University of Texas at San Antonio  (23642)

Principal Investigator: Forsthuber, Thomas

Total Amount of Contract, Award, or Gift (Annual before 2011): $ 591,566

Exceeds $250,000 (Is it flagged?): Yes

Start and End Dates: 4/1/14 <> 3/31/17

Restricted Research: YES

Academic Discipline: CIHR-PI-FORSTHUBER  

Department, Center, School, or Institute: South Texas Center for Emerging Infectious Diseases (STCEID)  

Title of Contract, Award, or Gift: M2 proteomics of the EAE model of multiple sclerosis

Name of Granting or Contracting Agency/Entity: National Multiple Sclerosis Society

Program Title: none

Note:

Despite the success in the treatment of acute episodes of multiple sclerosis (MS) much less progress has been made in treating and preventing disease progression to disability. Most MS patients go through multiple therapies due to a lack of sensitive and specific tests to determine whether treatments are effective and curtail disease progression. The objective of this proposal is to address a critical bottleneck in developing effective treatments for progressive MS by investigating protein biomarkers for disease progression in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In our own preliminary studies we have developed a novel quantitative microwave & magnetic (M2) proteomics method to quantify expression changes in key CNS proteins (and putative biomarkers) over the course of EAE (preliminary results). Furthermore, we have developed a method to induce EAE of predetermined severity using adoptive transfer EAE in combination with pre-transfer cytokine ELISPOT analysis. We have already identified several promising candidate protein biomarkers that correlate with EAE onset, peak, and remission (preliminary results). Importantly, we have preliminary results to show that predicted candidate protein biomarkers can be detected in serum of mice with EAE. The central hypothesis underlying this proposal is that disease progression of EAE can be followed in blood (serum) by expression changes of CNS disease-specific protein biomarkers. The rationale for the proposed research is to provide proof-of-principle for developing homologous biomarkers for disease progression in MS patients. We will test our central hypothesis with two specific aims. In Aim 1 we will determine by M2 proteomics key protein isoforms with altered expression in CNS tissue most indicative of progressive EAE. The set of key protein isoforms with altered expression in CNS tissue determined by this aim will be prioritized by statistics and bioinformatics methods to select suitable candidate protein biomarkers for detection in serum by the studies proposed in Aim 2. In Aim 2 we will determine which of the protein biomarkers most indicative of EAE progression are detectable in serum by M2 proteomics and immunoassays. Together, the studies proposed in the two aims will provide biomarkers for EAE progression in the EAE model and will advance our understanding of the mechanisms driving disease progression, will allow testing treatments aimed at preventing disease progression, and will form the basis for developing homologous markers in MS patients. We have already obtained preliminary results that the aims are feasible and are highly likely to provide important information.

Discussion: No discussion notes

 

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