***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Erythropoietin ( EPO ) derivatives have been found to increase frataxin levels in Friedreich 's ataxia ( FRDA ) in vitro . This multicenter , double-blind , placebo-controlled , phase II clinical trial aim ed to evaluate the safety and tolerability of Lu AA24493 ( carbamylated EPO ; CEPO ) . METHODS Thirty-six ambulatory FRDA patients harboring > 400 GAA repeats were 2:1 r and omly assigned to either CEPO in a fixed dose ( 325 µg thrice-weekly ) or placebo . Safety and tolerability were assessed up to 103 days after baseline . Secondary outcome measures of efficacy ( exploration of biomarkers and ataxia ratings ) were performed up to 43 days after baseline . RESULTS All patients received six doses of study medication . Adverse events were equally distributed between CEPO and placebo . There was no evidence for immunogenicity of CEPO after multiple dosing . Biomarkers , such as frataxin , or measures for oxidative stress and ataxia ratings did not differ between CEPO and placebo . CONCLUSION CEPO  was safe and well tolerated in a 2-week treatment phase . Secondary outcome measures remained without apparent difference between CEPO and placebo BACKGROUND AND PURPOSE A pilot study of high dose coenzyme Q(10 ) ( CoQ(10))/vitamin E therapy in Friedreich 's ataxia ( FRDA ) patients result ed in significant clinical improvements in most patients . This study investigated the potential for this treatment to modify clinical progression in FRDA in a r and omized double blind trial . METHODS Fifty FRDA patients were r and omly divided into high or low dose CoQ(10)/ vitamin E groups . The change in International Co-operative Ataxia Ratings Scale ( ICARS ) was assessed over 2 years as the primary end-point . A post hoc analysis was made using cross-sectional data . RESULTS At baseline serum CoQ(10 ) and vitamin E levels were significantly decreased in the FRDA patients ( P < 0.001 ) . During the trial CoQ(10 ) and vitamin E levels significantly increased in both groups ( P < 0.01 ) . The primary and secondary end-points were not significantly different between the therapy groups . When compared to cross-sectional data 49 % of all patients demonstrated improved ICARS scores . This responder group had significantly lower baseline serum CoQ(10 ) levels . CONCLUSIONS A high proportion of FRDA patients have a decreased serum CoQ(10 ) level which was the best predictor of a positive clinical response to CoQ(10)/vitamin E therapy . Low and high dose CoQ(10)/vitamin E therapies were equally effective in improving ICARS scores Background : Friedreich ’s ataxia ( FRDA ) , the most common genetic cause of ataxia , is characterised by progressive neurodegeneration and cardiomyopathy . Initial treatments are likely to slow progression rather than reverse morbidity . An appropriate and sensitive scale to measure disease progress is critical to detect the benefit of treatments . Objective : To compare the  Friedreich Ataxia Rating Scale ( FARS )  with other scales proposed as outcome measures for FRDA . Methods : 76 participants were assessed with the  FARS  and the  International Cooperative Ataxia Rating Scale ( ICARS )  and 72 of these participants were also assessed with the  Functional Independence Measure  and the  Modified Barthel Index .  43 participants had repeat measures at an interval of 12 months . Sensitivity and responsiveness were assessed using the effect size for each measure and the sample size required for a placebo-controlled clinical trial . Results : The FARS showed a high correlation with the other three measures . A significant change in the score over 12 months was detected by the FARS , the International Cooperative Ataxia Rating Scale and the Functional Independence Measure . The FARS had the greatest effect size and requires fewer patients for an equivalently powered study . Conclusions : Of the scales assessed , the FARS is the best to use in clinical trials of FRDA . This is based on effect size , and power calculations that show that fewer participants are required to demonstrate the same effect of an intervention . Further work is required to develop more sensitive and responsive instruments Background — This cross-sectional study provides a practical approach for the clinical assessment of Friedreich ataxia ( FA ) cardiomyopathy ( FA-CM ) . Methods and Results — A comprehensive cardiac assessment , including  st and ard echocardiography , color Doppler myocardial imaging , cardiac magnetic resonance imaging , ECG , and exercise stress testing  , was performed in 205 FA patients . To assess myocardial hypertrophy in FA-CM , the end-diastolic interventricular septal wall thickness ( IVSTd ) was found to be the best echocardiographic parameter compared with cardiac magnetic resonance imaging – determined left ventricular mass . With the use of this parameter , 4 groups of patients with FA-CM could be defined . Patients with normal values for IVSTd ( 31.7 % ) were classified as having no FA-CM . Patients with an IVSTd exceeding the predicted normal IVSTd were classified as having mild FA-CM ( 40 % ) if IVSTd exceeded the normal value by < 18 % or as having intermediate FA-CM ( 16.1 % ) if IVSTd exceeded the normal value by ≥18 % . Patients with ejection fraction < 50 % were classified as having severe FA-CM ( 12.2 % ) . In addition to increased myocardial mass , severe FA-CM was further characterized by dilatation of the left ventricle , reduced systolic strain rate of the posterior wall , and ECG abnormalities . Regional myocardial function correlated negatively with FA-CM groups . Younger patients had a tendency for more advanced FA-CM . Importantly , no clear correlation was found between FA-CM groups and neurological function . Conclusions — We provide and describe a readily applicable clinical grouping of the cardiomyopathy associated with FA based on echocardiographic IVSTd and ejection fraction data . Because no distinct interrelations between FA-CM and neurological status could be determined , regular follow-up of potential cardiac involvement in FA patients is essential in clinical practice . Clinical Trial Registration — https://www . clinical trials.gov . Unique identifier : NCT00905268 Genetic disorders of iron metabolism and chronic inflammation often evoke local iron accumulation . In Friedreich ataxia , decreased iron-sulphur cluster and heme formation leads to mitochondrial iron accumulation and ensuing oxidative damage that primarily affects sensory neurons , the myocardium , and endocrine gl and s. We assessed the possibility of reducing brain iron accumulation in Friedreich ataxia patients with a membrane-permeant chelator capable of shuttling chelated iron from cells to transferrin , using regimens suitable for patients with no systemic iron overload . Brain magnetic resonance imaging ( MRI ) of Friedreich ataxia patients compared with age-matched controls revealed smaller and irregularly shaped dentate nuclei with significantly ( P < .027 ) higher H-relaxation rates R2 * , indicating regional iron accumulation . A 6-month treatment with 20 to 30 mg/kg/d deferiprone of 9 adolescent patients with no overt cardiomyopathy  reduced R2 * from 18.3 s(-1 ) ( + /- 1.6 s(-1 ) ) to 15.7 s(-1 ) ( + /- 0.7 s(-1 ) ; P < .002 ) , specifically in dentate nuclei and proportionally to the initial R2 * ( r = 0.90 ) . Chelator treatment caused no apparent hematologic or neurologic side effects while reducing neuropathy and ataxic gait in the youngest patients . To our knowledge , this is the first clinical demonstration of chelation removing labile iron accumulated in a specific brain area implicated in a neurodegenerative disease . The use of moderate chelation for relocating iron from areas of deposition to areas of deprivation has clinical implication s for various neurodegenerative and hematologic disorders OBJECTIVE To assess the efficacy of idebenone on neurological function in patients with Friedreich ataxia . DESIGN R and omized , double-blind , placebo-controlled intervention trial . SETTING Children 's Hospital of Philadelphia and the University of California at Los Angeles . PARTICIPANTS Seventy ambulatory pediatric patients ( age , 8 - 18 years ) with a baseline International Cooperative Ataxia Rating Scale ( ICARS ) score of 10 to 54 . INTERVENTIONS Participants were r and omized into 1 of 3 treatment arms : 450 or 900 mg of idebenone per day ( in those with a body weight < or = or > 45 kg , respectively ; n = 22 ) ; 1350 or 2250 mg of idebenone per day ( n = 24 ) ; or placebo ( n = 24 ) . MAIN OUTCOME MEASURES Mean change from baseline to week 24 in ICARS score was the primary efficacy variable . Mean change in Friedreich Ataxia Rating Scale ( FARS ) score , performance measures , and activities of daily living were the secondary efficacy variables . RESULTS Patients who received idebenone improved by 2.5 points on mean ICARS score compared with baseline , while patients in the placebo group improved by 1.3 points . Patients who took idebenone also improved by 1.6 points on the FARS , while patients taking placebo declined by 0.6 points . For both end points , the difference between the idebenone and placebo groups was not statistically different . CONCLUSIONS Idebenone did not significantly alter neurological function in Friedreich ataxia during the 6-month study . Larger studies of longer duration may be needed to assess the therapeutic potential of drug c and i date s on neurological function in Friedreich ataxia . Trial Registration clinical trials.gov Identifier : NCT00537680 Fast breath-hold cardiovascular magnetic resonance ( CMR ) shows excellent results for inter study reproducibility of left ventricular ( LV ) volumes , ejection fraction , and mass , which are thought to be superior to results of 2-dimensional echocardiography . However , there is no direct comparison of the inter study reproducibility of both methods in the same subjects . A total of 60 subjects ( normal volunteers [ n = 20 ] , or patients with heart failure [ n = 20 ] or LV hypertrophy [ n = 20 ] ) underwent 2 CMRs and 2 echocardiographic studies for assessment of LV volumes , function , and mass . The inter study reproducibility coefficient of variability was superior for CMR in all groups for all parameters . Statistical significance was reached for end-systolic volume ( 4.4 % to 9.2 % vs 13.7 % to 20.3 % , p < 0.001 ) , ejection fraction ( 2.4 % to 7.3 % vs 8.6 % to 19.4 % , p < 0.001 ) , and mass ( 2.8 % to 4.8 % vs 11.6 % to 15.7 % p < 0.001 ) , with a trend for end-diastolic volume ( 2.9 % to 4.9 % vs 5.5 % to 10.5 % , p = 0.17 ) . The superior inter study reproducibility result ed in considerably lower calculated sample sizes ( reductions of 55 % to 93 % ) required by CMR compared with echocardiography to show clinical ly relevant changes in LV dimensions and function . Thus , CMR has excellent inter study reproducibility in normal , dilated , and hypertrophic hearts , and is superior to 2-dimensional echocardiography BACKGROUND Antioxidant therapy is a new therapeutical approach for patients with Friedreich ataxia . AIMS To assess the effectiveness of long-term idebenone treatment in Friedreich ataxia patients . METHODS An open-labelled prospect i ve study . Ten paediatric patients ( age range 8 - 18 years ) and 14 adults ( age range 18 - 46 years ) with genetic diagnosis of Friedreich ataxia were treated with idebenone ( 5 - 20mg/kg/day ) for 3 - 5 years . Neurological evolution was evaluated using the International Cooperative Ataxia Rating Scale ( ICARS ) , and cardiological outcomes using echocardiography . RESULTS In paediatric patients , no significant differences were observed in ICARS scores and echocardiographic measurements when comparing baseline status and after 5 years of follow-up . Concerning adult cases , ICARS scores showed a significant increase in neurological dysfunctions during 3 years of therapy ( Wilcoxon test , p=0.005 ) , while echocardiographic measurements remained unchanged . CONCLUSIONS Our results indicate that longer-term idebenone treatment prevented progression of cardiomyopathy in both paediatric and adult patients , whereas its stabilizing effect on neurological dysfunction was present only in the paediatric population , mainly before puberty . This suggests that the age at which idebenone treatment is initiated may be an important factor in the effectiveness of the therapy To determine the role of recombinant human erythropoietin as a possible treatment option in Friedreich 's ataxia , we performed an open‐label clinical pilot study . Primary outcome measure was the change of frataxin levels at week 8 versus baseline . Twelve Friedreich 's ataxia patients received 5,000 units recombinant human erythropoietin three times weekly subcutaneously . Frataxin levels were measured in isolated lymphocytes by enzyme‐linked immunosorbent assay . In addition , urinary 8‐hydroxydeoxyguanosine and 
    Output:
    
End-diastolic interventricular septal thickness showed a small decrease in the smaller of the two included studies .
There were no deaths related to the treatment with antioxidants .
A single study of idebenone provided low- quality evidence for a decrease in LVM , which is of uncertain clinical significance but of potential importance that needs to be clarified .
According to low- quality evidence , serious and non-serious adverse events were rare in both antioxidant and placebo groups .