A gene therapy method tested in human cells ‘significantly’ increased production of frataxin, the protein deficient in Friedreich's ataxia
Human cells treated with engineered transcription activation-like effector (TALE) proteins produced two to three times more frataxin protein than did control cells, a team of researchers has reported.
A deficiency of the frataxin protein is the underlying molecular cause of Friedreich's ataxia (FA). The deficiency is caused by mutations in the frataxin gene that make the genetic instructions for building the protein unavailable to cellular protein-building machinery.
Increasing frataxin protein production by two to three times is "significant," the researchers wrote, noting that people with FA produce only 5 to 30 percent of the amount of frataxin protein levels produced by people unaffected by the disease. Carriers (who have no symptoms of the disease) produce approximately 50 percent of normal frataxin levels. "Thus, for the majority of patients, an increase of two- to three-fold in the production of frataxin would represent a level of production comparable to that of carriers," the researchers note.
The new TALE protein-based gene therapy approach potentially could be used to provide an effective, long-term therapeutic strategy for treating FA.
Benefits for other diseases
The strategy likely could be effective in any disease in which a genetic mutation leads to decreased production of a protein but where the coding for the protein — and as a result, the protein's form and function — remains intact.
The approach also could work for diseases that may be ameliorated though an increase in the expression of a compensatory gene. (For example, utrophin protein production could be increased to help make up for the deficiency in dystrophin protein in Duchenne muscular dystrophy, or DMD.)
Complete study results were published online July 20, 2012, in Human Gene Therapy. To read the full report free of charge, see Transcription Activator-Like Effector Proteins Induce the Expression of the Frataxin Gene.