FARA continues to fund a robust research portfolio including drug discovery, cellular and animal model development, biomarker research and clinical studies. Monthly, we will spotlight grants funded through FARA's Scientific Grant Program with a summary of the research work. The following grants were all recently approved for their second year of funding.
The role of iron accumulation and increased lipid synthesis in the pathogenesis of Friedreich's ataxia
Hugo Bellen, Baylor College of Medicine, Houston, Texas
Dr. Bellen identified a fly mutant of frataxin that exhibits an age dependent neurodegenerative phenotype that can be rescued with the human frataxin gene, suggesting that the human and fly frataxin play a conserved role to maintain neuronal function. Kuchuan Chen, a graduate student in the Bellen lab, has shown that fly frataxin mutants exhibit a dramatic increase of iron deposits in multiple tissues. Reducing iron levels in food as well as neuronal activity suppresses the neurodegeneration, suggesting that iron accumulation and an impaired energy state contribute to the neurodegenerative phenotype. Furthermore, a drug that inhibits sphingolipid synthesis called myriocin significantly delayed the demise of neurons. They propose that aberrant iron deposits lead to an abnormal lipid homeostasis that causes toxicity. This project aims to investigate the mechanism of neurodegeneration in the fly frataxin mutant, which may identify new therapeutic strategies. Dr. Bellen has made important progress in his studies of the fly frataxin mutant phenotype in the first year of study. He proposes to expand his research to mice and patient samples (from CCRN Investigator- Dr. Martin Delatycki, Australia) in the second year, an essential step towards establishing the relevance of fly results to mammals.