Introduction: Friedreich’s ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a guanine adenine adenine (GAA) repeat expansion in the FXN gene that results in frataxin deficiency. Tissue frataxin concentrations are correlated with age of disease onset and inversely correlated with the number of GAA repeats and rate of disease progression. The range of the number of GAA repeats observed in the population of patients with FRDA results in a diverse spectrum of disease characteristics. The goal of this study was to describe the characteristics of adults with FRDA who participated in clinical studies evaluating nomlabofusp as a potential treatment for patients with FRDA.
Methods: Disease characteristics (e.g. age at onset, GAA repeat length) of adults with FRDA participating in Phase 1 and 2 nomlabofusp interventional studies were summarized and evaluated relative to baseline buccal and skin cell frataxin concentrations.
Results: Sixty-one subjects participated in at least one study; 18 participated in more than one study. Mean age was 31.9 years (range 19- 69). Mean age of onset was 15.9 years (range 5- 60). Mean (range) shorter and longer GAA repeat lengths were 555.8 (99- 1000) and 890.2 (265- 1300). Mean baseline modified Friedreich’s ataxia Rating scale neurologic score was 49.5 (13.2- 74.5). Mean (range) baseline buccal and skin cell frataxin concentrations were 1.90 (0.70- 4.95) and 3.25 (1.40- 8.10) pcg/mcg, respectively. There is a relationship between frataxin concentrations and age of onset and GAA repeat length. There is also a relationship between skin and buccal cell frataxin concentrations.
Discussion: Age of onset is associated with more rapid disease progression. Data from the nomlabofusp interventional studies are consistent with previously published data that suggest that lower tissue frataxin concentrations are associated with more rapid disease progression. Increasing frataxin concentrations in patients with FRDA may decrease rate of disease progression.
Conclusion: The study population in the nomlabofusp interventional studies is representative of the FRDA population, and tissue frataxin concentration data from these studies are consistent with prior studies demonstrating that lower frataxin concentrations are associated with earlier onset of disease. Buccal and skin cell frataxin levels correlate with each other.