Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial

@article{Prospero2007NeurologicalEO,
  title={Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial},
  author={Nicholas A. Di Prospero and Angela Baker and Neal O. Jeffries and Kenneth H. Fischbeck},
  journal={The Lancet Neurology},
  year={2007},
  volume={6},
  pages={878-886}
}
BACKGROUND Friedreich's ataxia (FA) is a progressive, multisystem, degenerative disorder caused by a reduction in frataxin. Loss of frataxin results in mitochondrial dysfunction and oxidative damage in patients and model systems. Previous studies have indicated that the antioxidant idebenone (5 mg/kg daily) reduces cardiac hypertrophy, but definite improvement in neurological function has not been shown. METHODS 48 genetically confirmed FA patients, aged 9-17 years, were enrolled in a 6-month… Expand

Paper Mentions

Interventional Clinical Trial
This study will determine whether a drug called idebenone is safe and effective in reducing the level of oxidants that are believed to damage the nervous system and hearts in patients… Expand
ConditionsFriedreich Ataxia
InterventionDrug
Combined Therapy with Idebenone and Deferiprone in Patients with Friedreich’s Ataxia
TLDR
Combined therapy with idebenone and deferiprone in patients with FDRA indicates a stabilizing effect in neurologic dysfunctions due to an improvement in the kinetic functions, with a worsening of gait and posture scores. Expand
Idebenone in Friedreich's ataxia
TLDR
The neurological function is in general not modified in adult patients, but a dose-dependent effect was demonstrated in young Friedreich's ataxia patients, and idebenone is well tolerated in paediatric and adult patients. Expand
Efficacy and safety of idebenone in the treatment of Friedreich ataxia: a review of early results and future prospects
TLDR
A Phase III trial has begun in the USA with the goal of assessing the efficacy of idebenone for the treatment of neurologic dysfunction in FRDA. Expand
Assessment of neurological efficacy of idebenone in pediatric patients with Friedreich's ataxia: data from a 6-month controlled study followed by a 12-month open-label extension study
TLDR
It is indicated that idebenone at a dose of 1,350/2,250 mg/day may offer a therapeutic benefit to pediatric FRDA patients by stabilizing the overall neurological function and improving fine motor skills and speech. Expand
IGF-1 in Friedreich’s Ataxia – proof-of-concept trial
TLDR
Results seem to indicate a benefit of this IGF-1 therapy to neurological functions in FRDA, as changes from baseline on the scale for the assessment and rating of ataxia, and by changes in echocardiogram parameters. Expand
Clinical experience with high-dose idebenone in Friedreich ataxia
TLDR
The results suggested that treatment with intermediate- and high-dose idebenone had beneficial effects on neurological symptoms, and two phase 3 trials have been initiated, one in the United States with young ambulatory patients and one in Europe without limits on age and disease severity. Expand
Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA).
TLDR
Idebenone did not decrease LV hypertrophy or improve cardiac function in subjects with FRDA and the present study does not provide evidence of benefit in this cohort over a 6-month treatment period. Expand
Double-blind, randomized and controlled trial of EPI-743 in Friedreich's ataxia.
TLDR
At 24 months, EPI-743 treatment was associated with a statistically significant improvement in neurological function and disease progression relative to a natural history cohort and was demonstrated to be safe and well tolerated. Expand
A phase 3, double-blind, placebo-controlled trial of idebenone in friedreich ataxia.
TLDR
Iebenone did not significantly alter neurological function in Friedreich ataxia during the 6-month study, and larger studies of longer duration may be needed to assess the therapeutic potential of drug candidates on neurologicalfunction in Fried reaxia. Expand
A0001 in Friedreich ataxia: Biochemical characterization and effects in a clinical trial
  • D. Lynch, S. Willi, +9 authors T. Sciascia
  • Psychology, Medicine
  • Movement disorders : official journal of the Movement Disorder Society
  • 2012
TLDR
Although A0001 did not alter the Disposition Index, it caused a dose‐dependent improvement in neurologic function, as measured by the Friedreich Ataxia Rating Scale, and longer studies will assess the reproducibility and persistence of neurologic benefit. Expand
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References

SHOWING 1-10 OF 25 REFERENCES
Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with Friedreich ataxia.
TLDR
Findings indicate that higher doses of idebenone lead to a proportional increase in plasma levels up to 55 mg/kg per day and that high-dose Idebenone is well-tolerated in patients with FA. Expand
Idebenone and reduced cardiac hypertrophy in Friedreich's ataxia
TLDR
There is a good case for giving idebenone continuously in a dose of 5–10 mg/kg/day in patients with Friedreich's ataxia at the onset of hypertrophic cardiomyopathy, as the drug has no serious side effects. Expand
Friedreich's ataxia: idebenone treatment in early stage patients.
TLDR
Idebenone treatment at early stages of the disease seems to reduce the progression of cerebellar manifestations and further blind trials with a greater number of patients and higher doses are needed to fully assess the therapeutic potential of idebenone in Friedreich's ataxia. Expand
Heart Hypertrophy and Function Are Improved by Idebenone in Friedreich's Ataxia
TLDR
An open trial of idebenone (oral supplementation; 5 mg/kg/day) in a large series of FRDA patients and followed their left ventricular mass and function, demonstrating the efficiency of Idebenone in controlling heart hypertrophy in FRDA. Expand
Idebenone delays the onset of cardiac functional alteration without correction of Fe-S enzymes deficit in a mouse model for Friedreich ataxia.
TLDR
The results support the view that frataxin is a necessary, albeit non-essential, component of the Fe-S cluster biogenesis, and indicate that Idebenone acts downstream of the primary Fe- S enzyme deficit, and support its utilization for the treatment of FRDA. Expand
Idebenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in age-related cognitive disorders.
TLDR
In view of the lack of a proven agent to limit or halt the progression of dementia in the elderly, idebenone may warrant consideration in patients with mild cognitive dysfunction on the basis of preliminary evidence of predominantly mild improvement of functional status in some patients and good tolerability. Expand
Oxidative stress in patients with Friedreich ataxia
TLDR
Oral treatment with 5 mg/kg/day of the antioxidant idebenone for 8 weeks significantly decreased urinary 8OH2'dG concentrations, indicating that 8OH 2'dG may be useful in monitoring therapeutic interventions in patients with FRDA. Expand
Idebenone treatment in Friedreich’s ataxia
TLDR
Idebenone reduced erythrocyte protoporphyrin IX levels in five of six patients with elevated baseline levels; however, changes did not consistently relate to cardiac improvement. Expand
A cellular model for Friedreich Ataxia reveals small-molecule glutathione peroxidase mimetics as novel treatment strategy.
TLDR
A cellular assay system is developed that discriminates between fibroblasts from FRDA patients and unaffected donors on the basis of their sensitivity to pharmacological inhibition of de novo synthesis of glutathione, and demonstrates for the first time that small-molecule GPX mimetics have potential as a novel treatment strategy for Friedreich Ataxia. Expand
Increased levels of plasma malondialdehyde in Friedreich ataxia.
TLDR
Several lines of evidence support the hypothesis that similar mechanisms are involved in the human disease, and data from yeast suggest that frataxin deficiency results in mitochondrial dysfunction and free radical damage. Expand
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