MSWA funded researcher Dr Sarah Rea is working towards a strategy for sporadic cases of Motor Neurone Disease (MND), a life-limiting neurological condition with no known treatment or cure.
Dr Rea’s research will investigate what happens when the interaction of two problematic proteins, P62 and TDP43, is prevented.
It is the interaction of these proteins, which are present in everyone, that becomes problematic for people living with MND.
Dr Rea said it was the displacement of TDP43 within the cells of someone diagnosed with Amyotrophic Lateral Sclerosis (ALS), the most common form of MND, which has a detrimental effect.
“In ALS cases TDP43 is situated and functions in the cytoplasm rather than the nucleus, meaning it is no longer able to perform its nuclear function,” said Dr Rea.
Dr Rea’s research looks into the role of another protein, P62’s, exposure to TDP43 and how this changes the position of TDP43 from the nucleus into the cytoplasm, causing it to become problematic.
“We know that P62 expression is doing these things to influence TDP43 to behave in a pathological way, so I wanted to look into how I can prevent this from happening.”
“What we have found so far is that by expressing P62 even at low levels it can draw TDP43 out of the nucleus and into the cytoplastic aggregates (clumps) that are thought to be pathogenic,” she added.
Dr Rea’s work will be conducted in three stages over the coming year.
“The first stage has identified which regions of P62 are involved in the process. Now we will be looking at developing interfering peptides to prevent the interaction between P62 and PTD43 to prevent that translocation away from the nucleus into the cytoplasmic aggregates,” said Dr Rea.
“The last stages of the research project will look at which different cellular stresses can be used to induce P62 expression and induce these changes to TDP43. We also want to find out more about cytoplasmic bodies and the effect of P62 variants on stress granule formation and disassembly.”
MSWA CEO Marcus Stafford AM said Dr Rea’s work was an invaluable component of MSWA’s research investment program, which reached a record $3 million in the 2018-19 year.
“Increasingly, MSWA has been allocating funds for research into other neurological conditions and with MND Day just around the corner, Dr Rea’s research is very relevant,” said Mr Stafford AM.
“We wouldn’t be able to do what we do without the generosity of our supporters. We are optimistic that through scientific research we can continue to search for causes, better treatments and hopefully one day, find a cure for neurological conditions like MND.”
Dr Rea said she was grateful to be funded by MSWA as it allows her to research her protein of interest, which she also studied as part of her honours degree and PhD which involved Paget’s Disease.
“I wouldn’t be able to do what I’m doing without MSWA. We’ve been able to employ someone to help me full-time in this project to allow me to continue working towards my fellowship.”
“Although we are only in the early stages, I have been really happy with the results so far and hope it will provide more pre-liminary data to help with future funding opportunities,” she added.
Dr Rea will be producing a research paper at the conclusion of her research and has submitted an abstract in hope of presenting at the International MND Conference which will be held in Perth later this year.