Development of a new treatment for MS progression
- Dr Edwin Lim, Macquarie University
- $255,000 over 2011 - 2014
- With support from The Trish Multiple Sclerosis Research Foundation
In this study, Dr Edwin Lim, will look at a different therapeutic target to break the vicious cycle of inflammation, cell damage, more inflammation and rapid progression that can occur in MS.
Inflammation is a critical progression factor in MS. The kynurenine pathway is known to be a key regulator of the human immune response and thus likely to play a role in both the inflammatory and autoimmune mechanisms involved in MS.
This is a three year project during which Dr Lim will aim to identify the various components of the kynurenine pathway involved in the pathogenesis of MS. The results from this innovative project are likely to lead to new diagnostic or therapeutic targets for MS.
Progress to Date
Tryptophan is a naturally occurring amino acid that is used by the body as one of the building blocks of protein. The pathway that breaks down tryptophan, the kynurenine pathway, is important in regulating the immune response in MS and leads to the production of several active metabolites which may be toxic to the brain.
Dr Lim’s results suggest that the kynurenine pathway is dysregulated in MS. He has shown that one particular neurotoxin associated with the pathway, is increased in MS and is showing promise as a potential biomarker to identify the different stages of MS. Biomarkers are particularly useful, for example, in clinical trials to quickly show whether new therapies are working to halt the disease.
After manipulating the kynurenine pathway in a laboratory model of MS, Dr Lim was able to limit the production of the toxic metabolites of the kynurenine pathway in the brain and reverse the progression of disease. This work indicates that altering kynurenine metabolism may be an important therapeutic approach for MS.
Work currently underway will examine the specific effect of these molecules on brain support cells. Dr Lim is completing the testing phase of the required techniques on cells grown in the laboratory and will now proceed to testing the effects in laboratory models of MS. This work should determine the underlying mechanism of the kynurenine pathway dysregulation in MS with results expected by the end of 2013.
- Chai (Edwin) K. Lim, Bruce J Brew and Gilles J. Guillemin. (2010) Understanding the roles of the kynurenine pathway in multiple sclerosis progression (Review). International Journal for Tryptophan Research 3:157-167.
- Nady Braidy, Chai (Edwin) Lim, Bruce Brew, Gilles J. Guillemin. (2013) Serum Nicotinamide Adenine Dinucleotide Levels Through Disease Course in Multiple Sclerosis. Brain Research (underway)