Significant advances in gene replacement therapy and the ability to edit genes have garnered much interest as a treatment approach for F A. There are several characteristics of FA that make it a favorable candidate for gene replacement therapy or gene editing approaches:
95% of individuals with F A have the same single gene mutation (GAA repeat expansion). Reducing the number of expansions by gene editing may results in normal expression of the gene
The mutation in the gene leads to gene silencing and thus a reduction of the frataxin protein, thus there are not abnormal or toxic proteins to remove
Individuals with F A do make some frataxin protein, just not enough, and therefore it is less likely that they will have an immune response to replacing frataxin
Individuals who are carriers for F A (one abnormal copy of the gene) only make 50% of normal frataxin and have no symptoms so even modest increases in frataxin are anticipated to be therapeutic
Newer generations of viral vectors, adeno-associated viruses, have improved safety profiles and have a favorable affinity for the tissues most affected in F A (brain, spinal cord, heart, muscle)