Interferon gamma may improve cardiac function in Friedreich's ataxia cardiomyopathy.

Keywords: Friedreich's ataxia Hypertrophic cardiomyopathy Interferon gamma Frataxin Freidreich's ataxia (FRDA) is an autosomal recessive hereditary disease with a prevalence of about 1 in 30,000, characterized by progressive neurologic impairment [1]. In addition, almost all patients have abnormal echocardiograms and more than 50% develop hypertro-phic cardiomyopathy [2]. Survival in FRDA is determined by cardiac complications, and progressive decline of left ventricular function is a negative prognostic factor [2]. The FRDA phenotype results from mutations (commonly an expanded GAA repeat sequence) attenuating expression of the FXN gene encoding frataxin, a mitochondrial protein involved in iron metabolism [3]. Thus, in FRDA, the frataxin protein is normal, but its expression level is reduced, resulting in mitochondrial dysfunction which leads to attenuated oxidative phosphorylation, increased oxidative stress, iron accumulation and inflammation [4]. In the heart, the result is a variable mixture of increased ventricular mass, replacement fibrosis, impaired myocardial perfusion, increased troponin levels and systolic as well as diastolic dysfunction. As yet there is no effective therapy for FRDA cardiomyopathy. However, small-scale trials of the antioxidant agents co-enzyme Q 10 and idebenone have reported modest beneficial effect on hypertrophy and systolic function [5]. Recently, interferon gamma (INFγ) was found to increase FXN gene expression in cells derived from FRDA patients, and to improve neurological function in FRDA mice [6]. Likewise, an open-label study of INFγ in children reported neurological improvement and minimal adverse reactions [7], and gene therapy restoring frataxin levels after the onset of heart failure in mice FRDA completely reversed the cardiomyopathy [8]. To the best of our knowledge, a possible therapeutic effect of INFγ on human FRDA cardiomyopathy has not been explored. Here, we report the effect of INFγ therapy in a single patient suffering from severe FRDA cardiomyopathy. At baseline, our female patient was 18 years old with a BMI of 21.9. She was diagnosed with severe hypertrophic cardiomyopathy with preserved systolic but attenuated diastolic function at the age of 9, and severe FRDA at the age of 10 with GAA expansion to appr. 700 repeats in both alleles. During the last couple of years, she had experienced several hospital admissions for heart failure with preserved ejection fraction. She used metoprolol, disopyramide, ivabradine, ibedenone, ranitidine, esomeprazole, and fluoxetine on a regular basis. Because of her poor cardiac condition, experimental INFγ therapy was considered advisable despite the lack of research evidence in humans. The patient consented to the treatment plan, which …