Meet The Researcher

Lachlan Rash

Dr Lachlan Rash

University of Queensland

Let's get started! Tell us an interesting fact about yourself.
I have been studying how animal venoms, particularly spider venoms, work in the body for 25 years. During the early 2000s, I spent three years training in a world class venom and ion channel research group in France. That was where I began my studies on acid-sensing ion channels (ASICs) and discovering new molecules that can modulate their activity to help understand what these ASIC channels do in the body and if they are good drug targets for several hard to treat diseases/conditions. It turns out that ASICs are important signalling molecules in nerves and contribute to learning processes in the brain and how we feel pain.
What inspired you to get involved in MS research?
When one type of these channels (ASIC1a) is overstimulated, it contributes to nerve cell death as happens in stroke and multiple sclerosis. One of the molecules I helped discover and characterise has very promising brain nerve protecting activity in animal models of ischemic stroke. Given that the process of nerve damage in stroke and multiple sclerosis has some similarities it makes sense to test the molecules that inhibit ASICs and are protective in stroke, in animal models of multiple sclerosis. This has never been done for the class of molecule on which we work.
Tell us about your current research project...
MS lesions are frequently associated with acidosis, which can over-activate ASIC1a and contribute strongly to nerve cell death. The nerve death is a main cause of impaired movement in MS. Our laboratory has developed a new drug candidate called Hi1a, which very strongly inhibits ASIC1. Hi1a has been shown to have strong neuroprotective effects in rodent models of stroke and spinal cord injury, but has not been tested in mouse models of MS. The overall goal of this project is to determine if specific inhibition of ASIC1a using our novel drug, can stop or reduce the nerve damage that is currently not well treated by available MS therapies. To do this we will test Hi1a and an improved version of this drug in a mouse model of progressive MS to determine if it can prevent the nerve damage.
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. 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 modification 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, being able to test an idea yourself and see if it is true, getting that positive result in real time, that is really exciting (assuming you have done all your control experiments properly and your 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 inspriation to keep trying, and making sure that those crucial control experiments are done just right!
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Dr Lachlan Rash