Friedreich's ataxia is an autosomal recessive progressive degenerative disorder caused by deficiency of the
protein frataxin. The most common genetic cause is a homozygotic expansion of GAA triplets within intron 1 of the
frataxin gene leading to impaired transcription. Preclinical in vivo and in vitro studies have shown that
interferon gamma (IFNγ) is able to up-regulate the expression of
frataxin gene in multiple cell types. We designed a phase IIa clinical trial, the first in Italy, aimed at assessing both safety and tolerability of IFNγ in Friedreich's patients and ability to increase
frataxin levels in peripheral blood mononuclear cells. Nine patients (6 female and 3 males aged 21-38 years) with genetically confirmed disease were given 3 subcutaneous escalating doses (100, 150 and 200 μg) of IFNγ (human recombinant
interferon 1 b gamma, trade name IMUKIN(®)), over 4 weeks. The primary end-point was the assessment of the safety and tolerability of IFNγ by means of standard clinical and hematological criteria. The secondary end-point was the detection of changes of
frataxin levels in peripheral blood mononuclear cells after each single escalating dose of the
drug. IFNγ was generally well tolerated, the main adverse event was
hyperthermia/
fever. Although, increases in
frataxin levels could be detected in a minority of patients, these changes were not significant. A large phase III multicenter, randomized clinical trial with IFNγ in
Friedreich's ataxia patients is currently ongoing. This study is expected to conclusively address the clinical efficacy of IFNγ
therapy in patients with
Friedreich's ataxia.