Coenzyme Q<sub>10</sub> and vitamin E deficiency in Friedreich’s ataxia: predictor of efficacy of vitamin E and coenzyme Q<sub>10</sub> therapy

Cooper, Jonathan M.; Korlipara, L.V. Prasad; Hart, Paul E.; Bradley, J. L.; Schapira, Anthony H.V.

doi:10.1111/j.1468-1331.2008.02318.x

Cited by 151 publications

(101 citation statements)

References 26 publications

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“…No effective treatment is currently available for most hereditary ataxias, and management remains supportive and symptomatic 12, 13. The rationale of this study stemmed from the observation that SCA38 is characterized by an increased amount of ELOVL5 protein with a mislocalization of the aberrant form in the Golgi apparatus and by a decrease of its final products, in particular DHA, in patients’ serum 5…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38

Manes

Alberici

Gregorio

et al. 2017

Annals of Neurology

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ObjectiveSpinocerebellar ataxia 38 (SCA38) is caused by mutations in the ELOVL5 gene, which encodes an elongase involved in the synthesis of polyunsaturated fatty acids, including docosahexaenoic acid (DHA). As a consequence, DHA is significantly reduced in the serum of SCA38 subjects. In the present study, we evaluated the safety of DHA supplementation, its efficacy for clinical symptoms, and changes of brain functional imaging in SCA38 patients.MethodsWe enrolled 10 SCA38 patients, and carried out a double‐blind randomized placebo‐controlled study for 16 weeks, followed by an open‐label study with overall 40‐week DHA treatment. At baseline and at follow‐up visit, patients underwent standardized clinical assessment, brain 18‐fluorodeoxyglucose positron emission tomography, electroneurography, and ELOVL5 expression analysis.ResultsAfter 16 weeks, we showed a significant pre–post clinical improvement in the DHA group versus placebo, using the Scale for the Assessment and Rating of Ataxia (SARA; mean difference [MD] = +2.70, 95% confidence interval [CI] = +0.13 to + 5.27, p = 0.042). At 40‐week treatment, clinical improvement was found significant by both SARA (MD = +2.2, 95% CI = +0.93 to + 3.46, p = 0.008) and International Cooperative Ataxia Rating Scale (MD = +3.8, 95% CI = +1.39 to + 6.41, p = 0.02) scores; clinical data were corroborated by significant improvement of cerebellar hypometabolism (statistical parametric mapping analyses, false discovery rate corrected). We also showed a decreased expression of ELOVL5 in patients’ blood at 40 weeks as compared to baseline. No side effect was recorded.InterpretationDHA supplementation is a safe and effective treatment for SCA38, showing an improvement of clinical symptoms and cerebellar hypometabolism. Ann Neurol 2017;82:615–621

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Section: Discussionmentioning

confidence: 99%

Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38

Manes

Alberici

Gregorio

et al. 2017

Annals of Neurology

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“…These are well reviewed elsewhere, and some examples are briefly reviewed below. 3,5,10,11,[26][27][28][29][30][31][32][33][34][35][36][37] Increased markers of oxidative stress have been demonstrated in neurodegenerative disease, including elevated levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) in Friedreich's ataxia (FA), amyotrophic lateral sclerosis (ALS), and PD. 32,35,[36][37][38][39][40] Elevated protein carbonyl formation and oxidized nitric oxide products with decreased glutathione peroxidase activity have been shown in ALS patients, while increased levels of malondialdehyde in plasma and decreased aconitase activities in cardiac and skeletal muscle have been shown in FA.…”

Section: Mitochondrial Dysfunction and Neurodegenerative Disease: A Rmentioning

confidence: 99%

“…50,89 A double-blind, randomized, but not placebo-controlled study of CoQ10 examined low versus high dose CoQ10 (30 mg versus 600 mg) in 50 FA patients. 31 The primary end-point was change in ICARS over two years, and again, cross-sectional data was used as a control group in lieu of a placebo arm. Serum CoQ10 levels were decreased at baseline in FA patients, and were significantly increased in both groups (3.4-fold in the low-dose group, 12.2-fold in the high-dose group).…”

Section: Friedreich's Ataxia (Fa)mentioning

confidence: 99%

Coenzyme Q10 effects in neurodegenerative disease

Spindler

Beal²,

Henchcliffe³

2009

NDT

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“…88 The benefit of coenzyme Q10 in combination with vitamin E has been seen in other neurodegenerative diseases with a primary mitochondrial defect (eg, Friedreich's ataxia). 89,90 Creatine has also been investigated in PD, and at a dose of 10 g daily was well tolerated and satisfied the predetermined criterion for nonfutility based on time to requirement for symptomatic therapy for 66 early PD patients. 91 Another blinded, placebocontrolled study of 2 g daily for 6 months then 4 g daily for 18 months in 31 PD patients compared with 17 placebo showed no significant differences compared with placebo.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Mitochondrial Pathology in Parkinson's Disease

Schapira

2011

Mount Sinai J Medicine

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The last 25 years have witnessed remarkable advances in our understanding of the etiology and pathogenesis of Parkinson's disease. The ability to undertake detailed biochemical analyses of the Parkinson's disease postmortem brain enabled the identification of defects of mitochondrial and free‐radical metabolism. The discovery of the first gene mutation for Parkinson's disease, in alpha‐synuclein, ushered in the genetic era for the disease and the subsequent finding of several gene mutations causing parkinsonism, 15 at the time of writing. Technological advances both in sequencing technology and software analysis have allowed association studies of sufficiently large size accurately to describe genes conferring an increased risk for Parkinson's disease. What has been so surprising is the convergence of these 2 separate disciplines (biochemistry and genetics) in terms of reinforcing the importance of the same pathways (ie, mitochondrial dysfunction and free‐radical metabolism). Other pathways are also important in pathogenesis, including protein turnover, inflammation, and post‐translational modification, particularly protein phosphorylation and ubiquitination. However, even these additional pathways overlap with each other and with those of mitochondrial dysfunction and oxidative stress. This review explores these concepts with particular relevance to mitochondrial involvement. Mt Sinai J Med 78:872–881, 2011. © 2011 Mount Sinai School of Medicine

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Coenzyme Q₁₀ and vitamin E deficiency in Friedreich’s ataxia: predictor of efficacy of vitamin E and coenzyme Q₁₀ therapy

Abstract: 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.

Cited by 151 publications

References 26 publications

Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38

Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38

Coenzyme Q10 effects in neurodegenerative disease

Mitochondrial Pathology in Parkinson's Disease

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Coenzyme Q10 and vitamin E deficiency in Friedreich’s ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy

Abstract: 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.

Cited by 151 publications

References 26 publications

Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38

Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38

Coenzyme Q10 effects in neurodegenerative disease

Mitochondrial Pathology in Parkinson's Disease

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Coenzyme Q₁₀ and vitamin E deficiency in Friedreich’s ataxia: predictor of efficacy of vitamin E and coenzyme Q₁₀ therapy