Research Grant Award

Sergio Cocozza, MD

University of Naples, Naples, Italy
Role of rhu-EPO and HDAC inhibitors alone and/or in combination on the regulation of frataxin expression. New prospective for FRDA treatment

Friedreich's ataxia is the consequence of frataxin deficiency. The relevance of the frataxin protein has been assessed in cellular models by showing that the phenotype can be completely reverted by the complementation of the protein. Unfortunately substitutive treatments as gene therapy approaches seem to be far away to be readily accessible within the near future. Under this point of view, drugs able to increase the frataxin amount are excellent candidates for a rationale approach to the FRDA therapy. But, up to now, although several drugs have been proposed, there still is no treatment available. It was recently demonstrated that both erythropoietin and HDAC inhibitors can increase the intracellular levels of frataxin in in-vitro models. HDAC inhibitors seem to increase the mRNA transcription while erythropoietin seems to increase only the protein amount. The mechanism by which erythropoietin acts in enhancing frataxin protein amount is not yet elucidated. The relevance of the erythropoietin as potential drug for Friedreich ataxia mainly is based on its availability as commercialized drug. Therefore it could be tested in patients without undergoing to long pharmaceutical and first phase clinical trials.

The present project is aimed to test the possible synergy between erythropoietin and a selected HDAC inhibitor, the 4B-BML-210-der.

We will perform tests in cellular models, in order to assess their efficacy alone and in combination and in order to find the best effective dose and administration timing. The results will be useful to plan further clinical trials.