A peptide given as a nasal spray might treat motor neurone disease, British scientists have suggested.
The scientists say they have identified a ground breaking way to block the transportation of mutant RNA and production of toxic repeat proteins that lead to the death of nerve cells in the most common forms of motor neurone disease.
Research by a team at the University of Sheffield’s Institute of Translational Neuroscience, showed that using a peptide to stop the transport of mutant repeated RNA molecules and production of toxic repeat proteins increases the survival of C9ORF72 nerve cells and protects them against neurodegeneration.
The findings build on a previous study by the team, finding that the abnormal transportation of the rogue RNAs copied from the C9ORF72 gene is caused by excessive stickiness of the SRSF1 cell transporter.
Rather than using conventional drugs, this study discovered that a small peptide incorporating a cell-penetrating module can stick to SRSF1 and effectively block the transportation of the rogue repeat RNA.
Writing in the latest Science Translational Medicine, the team says the peptide could be given to MND and frontotemporal dementia (FTD) patients orally as a nasal spray.
Study leader Professor Guillaume Hautbergue, professor of translational RNA biology at the University of Sheffield, said: “When we tested our innovative approach by adding the peptide to the food eaten by fruit flies not only did the peptides block the damaging mutations which cause MND and FTD from being transported to the cell’s nucleus, we actually saw an improvement in their 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.
“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.
“MND and FTD are devastating diseases which currently have no cure. This is a promising alternative to conventional small molecule drugs which are often limited by poor penetration of the blood-brain barrier.”
The researchers, which included collaborators from the University of Cambridge, the University of Leicester and ETH Zurich, hope this discovery will transform the future of clinical trials for the most common forms of MND and FTD within the next few years.
A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export suppresses neurodegeneration. Science Translational Medicine 1 March 2023.
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