Scientists have discovered a novel way to halt nerve cell death in the most common forms of motor neuron disease and frontotemporal dementia, which could transform how these neurodegenerative conditions are treated. What’s more, it has the ability to be delivered orally, so there’s even potential it could be packaged in a nasal spray.
The groundbreaking research out of the University of Sheffield’s Institute of Translational Neuroscience (SITraN) focuses on using a peptide with a cell-penetrating module to block the pathway of mutant repeated RNA molecules. When these rogue molecules migrate from the cell’s nucleus to the outer cytoplasm, they’re used to produce toxic repeat proteins that ultimately kill neurons, which fuels motor neuron disease (MND) and frontotemporal dementia (FTD) degeneration.
“This concept of using peptides to block destructive mutations unlocks such an exciting and innovative treatment pathway which until now has not been explored by scientists,” said Guillaume Hautbergue, professor of translational RNA biology at the University of Sheffield, who led the study.
Previously, the researchers had discovered that movement of the problem RNA copied from the C90RF72 gene – the most frequent cause of MND and FTD – was due to the excessive stickiness of the SRSF1 cell transporter. Their new peptide, made up of a small assembly chain of amino acids, penetrates cells to adhere to the SRSF1 transporter, blocking its export.
In clinical research with fruit flies, scientists even observed that when peptides sealed shut this cellular pathway, there was even an improvement in neurofunction.
“This means the peptide is effectively blocking the progression of the neurodegenerative condition and also helping to restore the function to the affected nerve cells,” said Hautbergue.
And researchers say the peptide could be given to MND and FTD patients orally, or via a nasal spray developed to enter the brain.
Both FTD – the most common cause of young onset dementia – and MND are debilitating, fatal conditions with little in the way of treatment to stop their rapid degeneration. This study opens the door for human trials and the development of non-invasive, targeted and effective medical intervention in the not-too-distant future.
“MND and FTD are devastating diseases which currently have no cure,” said Hautbergue. “This is a promising alternative to conventional small molecule drugs which are often limited by poor penetration of the blood-brain barrier.”
The study was published in Science Translational Medicine.
Source: University of Sheffield