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Molecule discovered by MRC researchers on path to drug development in neurodegeneration

16 Aug 2017

This case study forms part of our Investing for Impact report, looking at how MRC- funded research delivers impact. More can be found in the Investing for Impact section of our website.

A new molecule identified in 2015 by MRC-funded research has been patented and licensed by a start-up pharmaceutical company in France. Experiments in mice have shown that this molecule, called Sephin1, is able to prevent the formation of protein tangles that are a hallmark of neurodegenerative diseases.

Studying the underpinning mechanisms of neurodegeneration allows the research community to develop a rational approach towards discovering new treatments. One of the hallmarks of neurodegenerative disease is the accumulation of misfolded proteins, which lead to plaque formation. Our cells attempt to counteract this by activating a programme known as the unfolded protein response (UPR). Once activated, this programme halts the production of any new proteins, destroys misfolded proteins, and increases the production of ‘molecular chaperones’ that make sure proteins are folded correctly. But if this programme is active for too long, it can also lead to damage; our cells constantly need to replenish proteins so persistently halting the production of any and all new proteins can lead to the death of these cells. When nerve cells die because of this, it results in neurodegeneration.

But what if there was a way to selectively keep this programme active without any detrimental effects? In 2015, Dr Anne Bertolotti at the MRC Laboratory of Molecular Biology has identified a novel compound called Sephin1 that seems to be able to do just that. Early experiments with mice have shown that treatment with Sephin1 was able to mitigate the effects of these plaques for neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Charcot-Marie-Tooth disease. It is possible that Sephin1 could have a similar effect on other neurodegenerative diseases as well.

Sephin1 has been patented and licensed through the MRCT to InFlectis BioScience, a start-up company based in France. InFlectis BioScience has since raised €6 million to perform a clinical trial in humans using this drug (now named IFB-088) and it has also been given Orphan Drug status by the US Food and Drug Administration for treating Charcot-Marie-Tooth disease (a rare hereditary motor and sensory neuropathy).

By studying fundamental cellular processes involved in neurodegeneration, research such as this demonstrates that by understanding the mechanisms involved, it is possible to develop compounds that can effectively target these processes.

Award details: MC_U105185860

Image description: Dr Anne Bertolotti (left) and chemical structure of Sephin1 (right)

Categories

  • Categories: Research
  • Health categories: Neurological
  • Strategic objectives: Tissue disease and degeneration, Securing impact from medical research
  • Locations: Cambridge
  • Type: Impact story, Success story