Friedreich ataxia is a rare
neurodegenerative disorder caused by insufficient levels of the essential
mitochondrial protein frataxin. It is a severely debilitating disease that significantly impacts the quality of life of affected patients and reduces their life expectancy, however, an adequate cure is not yet available for patients.
Frataxin function, although not thoroughly elucidated, is associated with assembly of
iron-
sulfur cluster and
iron metabolism, therefore insufficient
frataxin levels lead to reduced activity of many mitochondrial
enzymes involved in the electron transport chain, impaired mitochondrial metabolism, reduced
ATP production and inefficient
anti-oxidant response. As a consequence, neurons progressively die and patients progressively lose their ability to coordinate movement and perform daily activities. Therapeutic strategies aim at restoring sufficient
frataxin levels or at correcting some of the downstream consequences of
frataxin deficiency. However, the classical pathways of
drug discovery are challenging, require a significant amount of resources and time to reach the final approval, and present a high failure rate.
Drug repositioning represents a viable alternative to boost the identification of a
therapy, particularly for
rare diseases where resources are often limited. In this review we will describe recent efforts aimed at the identification of a
therapy for
Friedreich ataxia through
drug repositioning, and discuss the limitation of such strategies.