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Trish Foundation contributes to first-ever discovery
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Progress Report on Fellowship to
Dr Edwin Lim  

Development of a new treatment for multiple sclerosis progression based on the alteration of tryptophan metabolism

The Trish Multiple Sclerosis Research Foundation, in partnership with MS Research Australia, has been supporting Dr Edwin Lim with a post-doctoral Fellowship since 2011. Dr Lim has been undertaking ground-breaking research into potential new therapeutic targets for alleviating the progression of MS.

Dr Lim, from Macquarie University in Sydney, has been using novel methods to investigate a metabolic pathway that is known to regulate immune activation and may be important in the chronic inflammation in the brain in progressive MS. This pathway is known as the kynurenine pathway, and it is a normal metabolic pathway used to break down amino acids (tryptophan) in the body. However, activation of this kynurenine pathway also produces break down products that, in excess, may be toxic to the brain - particularly the brain support cells that produce myelin.

Now, nearing the end of his four-year Fellowship, Dr Lim has studied people with MS as well as animal models of MS, in order to examine the role of kynurenine pathway in producing inflammation and identify which components of the kynurenine pathway are most important in MS. The results from this innovative project are likely to lead to new diagnostic or therapeutic targets for MS.

Early results from Dr Lim’s work established an important basis for the potential role of the kynurenine pathway in MS, showing that a neurotoxin (chemical toxic to nerve cells) produced as a by-product of the kynurenine pathway is increased in people with MS, and may be associated with increasing severity of illness progression.

Next, using healthy laboratory-grown cells, Dr Lim demonstrated that blocking the kynurenine pathway can lead to reduced production of neurotoxic metabolites, and reduced the damage to myelin-producing cells. Dr Lim then extended this work to show that the same was true in living organisms. Manipulating the kynurenine pathway in mice with MS-like disease was still able to limit neurotoxicity, and actually reduced disease severity in the mice.

In the final stages of this work in 2014, Dr Lim will use genetic techniques to try and identify the key molecules involved in this effect. These molecules could then provide a potential target for future work to explore the development of new therapies for people with MS.

Dr Lim’s work to date has been extremely productive, resulting in two publications and a book chapter, with one additional manuscript currently submitted for publication, and further three in preparation. This work represents a very exciting advance in our understanding of the molecular causes of inflammation in MS and has huge potential for future therapeutic development.

Trish Foundation & MS Research Australia Working together to find a cure for MS
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