Meet The Researcher

Lachlan Rash

Dr Lachlan Rash

The University of Queensland, QLD

Let's get started! Tell us an interesting fact about yourself.
During my final year of high school I would distract myself from studying by catching flies and feeding them to the black spiders that lived in the flocky webs around my bedroom window. It was the venom of these black house spiders that ended up being the focus of my Honours research project and started a 25-year career studying spider venoms.
What inspired you to get involved in MS research?
One of the molecules we discovered and characterised from an Australian funnel web spider (Hi1a) has very promising brain nerve protecting activity in animal models of stroke and it even protects the heart from heart attack damage. The target of this venom peptide is acid-sensing ion channel 1a (ASIC1a) and it seems to play a big role in nerve damage and inflammation in the central nervous system. Given that the process of nerve damage and inflammation in stroke and multiple sclerosis have many similarities, it makes sense to test the molecules that are protective in stroke, in models of multiple sclerosis. This has never been done for the class of molecules on which we work.
What do you think has been the most exciting development in MS research?
MS is traditionally thought to be caused by a collection of circumstances that result in the peripheral immune system gaining access to and attacking the myelin sheath of nerves of the central nervous system. Many clinical drugs can now target this process and provide benefit to a lot of people, but unfortunately, they do not stop the disease. Recent research is suggesting that the cause of MS could come from within the central nervous system itself. This changes the focus of research efforts to look more at cells in the central nervous system as new therapeutic targets to slow or stop disease progression and hopefully promote the repair of damaged nerves.
Tell us about your current research project...
Multiple sclerosis lesions are frequently associated with acidosis, which can over-activate ASIC1a and contribute strongly to nerve cell death and increase inflammation. The nerve death is a main cause of impaired movement in MS. Research at the University of Queensland and Monash University has resulted in a new drug candidate called Hi1a, which very strongly inhibits ASIC1. Hi1a has neuroprotective effects in rodent models of stroke and spinal cord injury, but has not been tested in animal models of MS. The overall goal of this project is to determine if specific inhibition of ASIC1a using our novel drugs, can stop or reduce the nerve damage and decrease the activity of central inflammatory cells that is currently not well treated by available MS therapies. To do this we will test Hi1a and several other drugs that inhibit ASIC1a in two mouse models of progressive MS to determine if it can prevent the nerve damage. We will also use patient tissue samples to see if this novel drug target is the same in humans.
Why is your research important and how will it influence the understanding and treatment of MS?
Despite great progress in drug development and approvals for the inflammatory component of multiple sclerosis, there are no clinically approved drugs that stop or slow the debilitating progressive neurodegeneration. Data from other research groups using non-selective drugs that block ASICs has shown that ASICs do play a role in the disease progression of MS, but the drugs used are not good enough to be effective in patients. The study we will carry out will confirm if inhibiting ASIC1a protects the nerves and myelin sheath from dying. This will help highlight ASICs as new drug target in MS. The study will also tell us if the modifications we have made to Hi1a improves its behaviour as a drug like molecule.
What do you enjoy most about working in the lab and what are some of the challenges you face?
There are several things that make working in a lab very rewarding and sometimes really exciting. Doing an experiment that reveals a new piece of knowledge or makes substantial progress on your favourite project. Getting a positive result in real time that shows your idea or theory might be true, that is truly exciting (assuming you have done all your experiments properly and the results are real that is!!). And most importantly, knowing that the work you are doing may ultimately help a lot of people lead better and more comfortable lives. This is a great motivation and inspiration to keep trying. A major challenge is getting adequate research funding to carry out the research. We are very lucky and grateful to have been awarded a grant from MS Australia to helps us do our research and hope we can report some promising results in the not-too-distant future.
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Lachlan Rash