Marek Napierala, assistant professor of molecular carcinogenesis at the MD Anderson Cancer Center of the University of Texas, Smithville, was awarded an MDA research grant totaling $320,451 over a period of three years to develop new models of Friedreich’s ataxia (FA) and explore new therapeutic approaches for the disease.
FA is caused by an increase in the number of short DNA sequences, termed GAA repeats, within a gene that encoded for the frataxin protein. This reduces the amount of frataxin that can be made in cells, a problem especially important in neurons (nerve cells) and heart muscle cells. These cells die during the course of the disease, leading to the symptoms of FA.
Napierala studies DNA-editing enzymes called zinc finger nucleases (ZFNs) that can target specific DNA sequences and, operating like a pair of molecular scissors, cut out disease-causing mutations. He will develop cell lines from patients with FA, and then use this technology to repair the gene within the cells.
“Editing the genome of FA cells via excision of the pathogenic expanded GAA repeats,” Napierala says, “will generate a perfect model system: ‘Patient neurons’ can be compared to ‘corrected patient neurons’ derived from the same individual, thus eliminating troublesome variability associated with analyses of patient/control pairs from separate, genetically different individuals.”
The technique will allow him to explore how cells respond when the defect is corrected, and to look for new targets for therapeutic intervention in the disease. In addition, it will establish methods that may be used for similar purposes in other repeat diseases, including myotonic muscular dystrophy (MMD or DM).
Funding for this MDA grant began Feb. 1, 2013.