Taking the STING out of MND

October 07, 2020

Melbourne researchers are working towards a potential treatment to slow the progression of motor neuron disease (MND), offering hope to people with this debilitating and incurable illness.

The research team have uncovered how inflammation in MND is triggered. Pinpointing the molecules involved in this pathway could be a first step towards a new treatment for MND.

They found that by blocking an immune sensor called STING, they could dramatically prevent inflammation from MND patient cells, paving the way for a new class of drugs to be developed for people with neurodegenerative disorders, such as MND.

The discovery, published today in Cell, was led by Walter and Eliza Hall Institute researchers Associate Professor Seth Masters and Dr Alan Yu, with colleagues from the University of Melbourne and Hudson Institute.

At a glance Halting the inflammatory response

MND is an incurable condition in which the nerve cells controlling the muscles that enable us to move, speak, swallow and breathe, fail to work. One in 10,000 Australians will be diagnosed with MND in their lifetime and the average life expectancy from diagnosis is just two years.

Most people suffering from MND have an accumulation of a protein called TDP-43 within cells of the central nervous system. This build-up is associated with an inflammatory response that precedes major symptoms of MND.

Institute researchers investigated how the disease-causing inflammation is triggered in MND, said Associate Professor Masters. "This unexpectedly identified that an immune sensor called STING is activated downstream of TDP-43. Fortuitously, our team had already studied the role of STING in other inflammatory diseases and are now working out how to block it."

The team then used new inhibitors - drug-like compounds - to block different components of this inflammatory pathway.

"Using cells from patients with MND that we can turn into motor neurons in a dish, we showed that blocking STING dramatically prevented inflammation and kept the cells alive longer. This is an exciting first step before taking these inhibitors into the clinic for treatment for MND.

Vital first step towards a treatment

Associate Professor Masters said his research had also established activation of STING in people who had passed away due to MND.

"We are now aiming to validate a biomarker of the pathway earlier in the disease progression. Once this neuroinflammatory biomarker is validated, we will better understand which patients will benefit the most from treatments targeting the pathway," he said.

"With this knowledge, there is the potential to develop a treatment for patients with MND.

"Interestingly, our preclinical models suggest that although the anti-inflammatory drugs that inhibit STING did not prevent disease onset, they did slow the degenerative progression of disease."

Hope for people with MND and other neurodegenerative disorders

Associate Professor Masters said this discovery offered hope for people diagnosed with the debilitating condition.

"We are hopeful this research could lead to a treatment for people with established MND, who currently have very few treatment options and a life expectancy post diagnosis of just two to five years," he said.

"While it isn't a cure, we hope it might extend life expectancy and dramatically improve the quality of life for people diagnosed with MND."

Associate Professor Masters said a future treatment might also be effective in slowing the progression of other neurodegenerative disorders.

"We are hoping to develop a new class of drugs that would act as STING inhibitors to stop the progression of neurodegenerative disorders, such as MND, Frontotemporal Dementia and Parkinson's disease."
-end-
The research was funded by the Australian National Health and Medical Research Council, veski, HHMI-Wellcome Trust, the Sylvia and Charles Viertel Foundation (SLM), the Australian Research Council, Fellowship Fonds de recherche du Québec-Santé, the WEHI Centenary Fellowship and Ormond College's Thwaites Gutch Fellowship in Physiology, the Motor Neurone Disease Research Institute of Australia, the Australian Phenomics Network, the Ian Potter Centre for Genomics and Personalized Medicine and the Victorian Government.

Walter and Eliza Hall Institute

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.