Progress Report on Fellowship to
Dr Edwin Lim
of a new treatment for multiple sclerosis progression based on the alteration
of tryptophan metabolism
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.
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