Dr Sarah Rea, who leads Functional Genomics at Murdoch University’s Centre for Molecular Medicine and Innovative Therapeutics and the Perron Institute, was recently awarded $100,000 by the State government to progress a vital project that could result in a much needed treatment for amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTD), a type of dementia. 

The funding came through the WA Near-miss Awards Ideas Grants 2021 program which provides support for WA researchers who narrowly missed out on a highly sought-after National Health and Medical Research Council Ideas Grant in 2021.  

The project will see Dr Rea and her team test two gene therapy strategies that aim to prevent the interaction of key proteins, TDP-43 and p62, found in both ALS and FTD sufferers. 

Normally TDP-43 is present in the nucleus of the cell, but in ALS and FTD the protein has problems with structure, location and aggregation that are thought to be critical to the pathogenesis of the diseases. 

Increased levels of the p62 protein also found in ALS and FTD tissues cause TDP-43 proteinopathy in neurons and lead to reduced nuclear function and changes to gene/RNA regulation. 

Dr Rea’s proposed therapies target a specific region of the p62 protein that mediates p62-induced TDP-43 proteinopathy. 

“We hypothesise that by preventing the interaction between p62 and TDP-43 we may be able to rescue and/or prevent TDP-43 proteinopathy from occurring, and this could thereby serve as a potential therapeutic strategy for ALS and FTD,” she said. 

Dr Rea will now use ALS patient-derived motor neurons to test the hypothesis and expects to have preliminary results by mid-2023. 

“Growing and differentiating induced pluripotent stem cells into motor neurons is very expensive and time consuming,” Dr Rea said. 

“This funding means that my team can progress this project to the next level. 

“If our gene therapy strategies are successful in patient-derived motor neurons, then this will provide the proof-of-concept required to obtain the funding needed for studies in preclinical models of ALS, and then hopefully clinical trials.” 

Article courtesy Murdoch University.