One approach to treating F A would be to supply functional frataxin genes or protein molecules to the person with F A through the insertion of functional genes to compensate for nonfunctional ones. Various gene therapy-based strategies hold the potential to benefit individuals with F A. Although it’s relatively early in the game, a limited number of studies in mice and human cells have yielded some encouraging results.
In a 2005 study, researchers used lentiviral or adeno-associated viral (AAV) vectors to carry the human frataxin gene into fibroblasts (cells that mature into a variety of connective tissue types) from F A patients. (A vector is a delivery vehicle for therapeutic genes.) Results included increased frataxin protein levels and a reduction in the treated cells’ sensitivity to oxidative stress. A 2007 study analyzed the feasibility of gene insertion via the emptied-out shell of the herpes simplex virus type 1 (HSV-1), partnered with a stretch of DNA called an amplicon that helps the vector target a specific cell type. Results in F A-affected mice and human cells showed highly efficient DNA transfer and increased levels of frataxin production.
Similar positive results in 2007 came from a Spanish study in which mice were engineered so that researchers could eliminate, or “knock out,” frataxin activity specifically in motor neurons. The mice developed neurological symptoms after four weeks, but achieved full recovery in as few as four weeks after receiving injections of HSV-1 amplicon vectors carrying DNA that codes for human frataxin. A Spanish study published in 2010 describes the successful use of artificial chromosomes and similar constructs called episomes to act as vectors for transporting genes to their targets.