Therapeutic Use of Interferon Gamma in Friedreich Ataxia

Abstract

Friedreich’s ataxia (FRDA) is a progressive neurodegenerative disorder caused by GAA triplet expansion in the FXN gene. At the cellular level, FRDA is associated with the deficiency of frataxin, a mitochondrial protein that plays a fundamental role in iron homeostasis and in the management of oxidative stress. The disease onset is usually in adolescence, leading to progressive disability. There is still no treatment to cure or halt the disease. Over the years an increasing number of drugs have been tested targeting different parts of the pathological cascade. One of the drugs tested has been interferon-gamma (IFN-γ). IFN-γ is currently approved for the treatment of chronic granulomatous disease and severe malignant osteopetrosis. In patients with FRDA, IFN-γ upregulated frataxin levels in cells from FRDA patients and increased frataxin expression in dorsal root ganglia neurons. In this chapter we review the basic science behind the proposal of IFN-γ as a potential treatment for FRDA and summarize the clinical studies related to the use of IFN-γ in FRDA, outlining critical lessons that have been learned in terms of drug efficacy and tolerability.