Ataxia UK Funds Work Into Compounds to Replace or Enhance Frataxin in Cells

Ataxia UK has awarded a £26,000 grant to advance research into compounds that can replace or boost the activity of frataxin, the protein that is lost in people with Friedrich’s ataxia (FA), the charity announced in a tweet.

Led by Benoit D’Autreaux, PhD, at the University of Paris-Saclay, the research project will use an assay, recently developed by D’Autreaux and his team, that measures frataxin activity without resorting to cells. The team plans to screen at least 100,000 different compounds to identify potential treatment candidates for FA.

FA is a neurodegenerative disease caused by a mutation in the FXN gene, which provides the instructions for making the frataxin protein. While its role is not fully understood, frataxin is needed for the normal functioning of nerve and muscle cells.

These mutations — which normally result in 90%–95% less frataxin in cells — cause problems with muscle coordination, or ataxia. Sometimes slurred speech, foot deformities, and a curved spine are also found in patients.

Gene therapy approaches that help cells produce normal amounts of frataxin, and other therapies that make up for the loss of this protein, are currently under development for FA. But no approved treatments currently are available to slow disease progression.

With this funding, worth about $33,600, D’Autreaux and colleagues aim to develop treatments that either replace the frataxin protein in cells, or enhance the function of available frataxin to restore cell health.

This research became possibly with the recent development of a new assay by the team that measures the activity of frataxin, or how well it functions. This assay followed the researchers’ discovery that frataxin accelerates the formation of iron and sulfur clusters in cells.

Previously, the activity of frataxin could only be monitored using cells. The new assay has no need for cells, allowing researchers to test molecules that directly target FA’s primary cause. This test is also much faster, enabling scientists to screen several thousand molecules in a short amount of time.

In this way, those compounds with the best therapeutic potential will be investigated, streamlining the drug development process.

After promising treatment candidates are identified, researchers will test them in animal models of FA, and potentially make further modifications to improve their safety and effectiveness.