CENTRAL TIME ZONE

Explore a past NAF research grant awardee’s funded study, gaining scientific insights about their Ataxia research.

Dr. Jacques P. Tremblay, will present the research, “Development of a Gene Therapy Approach for Friedreich’s Ataxia by Deletion of GAA Expansion in the Frataxin Gene.”

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Research Lay Summary: Friedreich ataxia is due to an increased number of the GAA repeats (GAAr) in a part of the frataxin gene. This reduces frataxin to 5-35% of normal levels. This induces coordination and cardiac problems, and premature death. I am proposing a direct treatment of the cause of the disease: i.e., the removal using the CRISPR/Cas9 technology of that GAAr. This will leave the frataxin gene under its natural control and this will not increase the number of frataxin genes in a given cell. Thus, there will not increase the expression of frataxin above the normal level in some cells. This is important because too high expression of frataxin is toxic for the cells.

My group has recently demonstrated that the new mouse model called YG8-800 (developed by the Jackson laboratory) containing 800 GAA repeats is an excellent model of Friedreich ataxia because it has a lower expression of frataxin and more severe symptoms.

My laboratory is currently trying to identify the best Cas9 protein to cut the frataxin gene before and after the GAAr to delete it from mouse and human cells in culture. We will also verify whether the CRISPR treatment is inducing unwanted cuts in other genes.

We are currently trying to identify the best vector (i.e., Adeno Associated Virus (AAV), lipid nanoparticles (LNPs), extra-cellular vesicles (EVs), engineered virus like particles (eVLPs) and chitosan nanoparticles (CN)) to deliver to the YG8-800 mouse model the components of the CRISPR technology (i.e., Cas9 and sgRNA).

The current experiments will permit to obtain results in a Friedreich mouse model that will lay the foundation for a completely new treatment of Friedreich ataxia.

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