World News – UA – Exit STING from MND


The research team discovered how inflammation in MND is triggered Identifying 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 drastically prevent inflammation in cells in patients with MND, 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 researchers at Walter and the Eliza Hall Institute, associate professor Seth Masters and Dr Alan Yu, along with colleagues from the University of Melbourne and from the Hudson Institute

MND is an incurable condition in which the nerve cells controlling the muscles that allow us to move, speak, swallow and breathe, do not work One in 10,000 Australians will be diagnosed with MND in their lifetime and average life expectancy after diagnosis is only two years

Most people with MND have a build-up of a protein called TDP-43 in central nervous system cells This build-up is associated with an inflammatory response that precedes the main symptoms of MND

Researchers at the institute studied how disease-causing inflammation is triggered in MND, said a Masters associate professor. “This unexpectedly identified that an immune sensor called STING is activated downstream of TDP -43 Fortunately, our team had previously studied the role of STING in other inflammatory diseases and are now working to block it »

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

“Using cells from MND patients that we can turn into motor neurons in a dish, we have shown that blocking STING significantly prevents inflammation and keeps cells alive longer. ‘an exciting first step before bringing these inhibitors into the clinic for the treatment of MND

Associate Professor Masters said his research has also established activation of STING in people who have died from MND disease

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

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

« We hope this research could lead to treatment for people with established MND, who currently have very few treatment options and a post-diagnosis life expectancy of only two to five years, » a- he declared

« Although it is not a cure, we hope it will extend life expectancy and dramatically improve the quality of life for people with MND »

Associate Professor Masters said that future treatment may also be effective in slowing the progression of other neurodegenerative disorders

« We hope to develop a new class of drugs that act as inhibitors of STING to stop the progression of neurodegenerative disorders, such as MND, frontotemporal dementia and Parkinson’s disease »

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, the Fellowship Fonds de recherche du Québec- Health, Ormond College’s WEHI Centenary Fellowship and Thwaites Gutch Fellowship in Physiology, the Motor Neuron Disease Research Institute of Australia, the Australian Phenomics Network, the Ian Potter Center for Genomics and Personalized Medicine and the Government of Victoria

Motor neuron disease, research, neuron, Melbourne, medicine, inflammation

News from the world – UA – Getting the STING out of the MND


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