World News – UA – Inflammation Trigger in Motor Neuron Disease Discovered

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Together with colleagues at the Walter and Eliza Hall Institute (WEHI) and the University of Melbourne, scientists at the Hudson Institute have revealed how inflammation in motor neuron disease (MND) is provoked, which could be the first step towards a new treatment

The research team has identified molecules involved in the inflammatory pathway to work on a potential treatment that could slow the progression of MND – offering hope to people with the incurable and debilitating disease

Scientists found that by blocking an immune sensor called STING, they could significantly prevent inflammation of the patient’s motor neurons (the cells destroyed by MND), thereby promoting the survival of the motor neurons This discovery lays the groundwork for a potential new class of drugs for people with neurodegenerative disorders, including motor neuron disease

The discovery, published in Cell, was led by researchers at the Walter Institute and Eliza Hall Institute, Associate Professor Seth Masters and Dr Alan Yu, along with colleagues from the University of Melbourne and Dr Michael Gantier, Hudson Medical Research Institute scientist

Study co-author Dr Gantier said: “The immune sensor STING and its inflammatory pathway are normally involved in protecting against viruses and bacteria, but they can also be activated in damaged cells.

« Our work discovered how the build-up of a protein called TDP-43 – which occurs in most people with motor neuron disease – causes the STING pathway to activate. This leads to persistent inflammation in the brain , which has devastating effects on brain function

« The study also shows that blocking the immune sensor STING with a drug-like compound can stop the progression of MND. This opens the door to the development of therapies to help slow the progression of other neurodegenerative diseases where the STING inflammatory pathway is involved

« Importantly, these results further indicate that the STING inflammatory pathway is probably a key factor in other neurodegenerative diseases, as recently suggested for Parkinson’s disease »

Motor neuron disease is an incurable disease in which the nerve cells controlling the muscles that allow us to move, speak, swallow and breathe do not work One in 10,000 people in Australia will be diagnosed with MND during of his life and the average life expectancy after diagnosis is only two years

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

WEHI researchers studied how disease-causing inflammation is triggered in MND, said A / Prof Masters “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 « 

A / Prof Masters said his research also established activation of STING in people who died from MND

« 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 »

Dr Michael Gantier and his laboratory have recently identified several preclinical and ready-to-use drugs that can block the STING inflammatory pathway. His team is now starting to study, with collaborators including A / Prof Masters, whether these drugs can be used in a variety of settings where the STING pathway is a key factor in disease, including chronic obstructive pulmonary disease, sepsis, fatty liver disease, autoimmune diseases such as systemic lupus, in addition to MND

These studies have the capacity to be quickly translated into effective treatment options for the thousands of people with MND and these other diseases

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

Motor neuron disease, neuron, inflammation, research

News from the world – UA – Inflammation trigger discovered in motor neuron disease


SOURCE: https://www.w24news.com

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