In a recent study, researchers from the University of Melbourne revealed the mechanism of Inflammation that slows the onset of motor neuron Disease (MND), thereby providing hope for people suffering from this debilitating and incurable disease.

They found that by blocking immune receptor Sting, they can significantly prevent inflammation in cells of MND patients, paving the way for the development of new drugs for neurodegenerative diseases such as MND.

The discovery was recently published in the journal Cell and was led by Associate Professor Seth Masters and Yulan Dr, researchers at the Walter and Eliza Hall Institute, and colleagues from the University of Melbourne and the Hudson Institute.

MND is an incurable disease characterized by difficulty speaking, swallowing, and breathing, and unable to work normally. The average life expectancy after diagnosis is only two years.

Most people with MND accumulate a protein called TDP-43 in the cells of the central nervous system. This accumulation is related to the inflammatory response before the main symptoms of MND.

Researchers at the Institute investigated how the disease-causing inflammation in MND is triggered. “We found that an immunosensor called STING is activated downstream of TDP-43. Fortunately, our team has studied the role of STING in other inflammatory diseases and is now studying how to stop it.”

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

“Using cells from MND patients can be transformed into motor neurons in a petri dish, we show that blocking STING can significantly prevent inflammation and make cells survive longer.” This is the first step to bring these inhibitors into the clinical treatment of MND.

Reference

Chien-Hsiung Yu et al, TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS, Cell (2020). DOI: 10.1016/j.cell.2020.09.020