On the question of GeneTAC selectivity, Shah pointed to preclinical work across multiple FA patient-derived cell types. He said GeneTAC molecules increased endogenous frataxin RNA and led to downstream effects including normalization of protein levels and improvements in functions such as cis-aconitate and cellular respiration. He added that exposure of wild-type genotype cells to an FA GeneTAC molecule had no impact because the repeat number in the wild-type allele is short and therefore does not produce a functional consequence when treated.
Patient population and endpoints in the FA study
Shah described RESTORE-FA enrollment criteria as “pretty permissive” beyond genetic confirmation of FA, including ambulatory and wheelchair-bound patients. He said the current study explores both IV and subcutaneous (sub-Q) administration to help determine dose route, dosing interval, and the frataxin response to inform future clinical investigation. While functional assessments are customary in FA trials and are being performed, he said the primary goal of the study is to look for a frataxin response.
