Treatment for mitochondrial disorders

 

Abstract

Background

Mitochondrial respiratory chain disorders are the most prevalent group of inherited neurometabolic diseases. They present with central and peripheral neurological features usually in association with other organ involvement including the eye, the heart, the liver, and kidneys, diabetes mellitus and sensorineural deafness. Current treatment is largely supportive and the disorders progress relentlessly causing significant morbidity and premature death. Vitamin supplements, pharmacological agents and exercise therapy have been used in isolated cases and small clinical trials, but the efficacy of these interventions is unclear.

Objectives

To determine whether there is objective evidence to support the use of current treatments for mitochondrial disease.

Search methods

We searched the Cochrane Neuromuscular Disease Group trials register (searched September 2003), the Cochrane Central Register of Controlled Trials, MEDLINE (January 1966 to October 3 2003), EMBASE (January 1980 to October 3 2003) and the European Neuromuscular Centre (ENMC) clinical trials register, and contacted experts in the field.

Selection criteria

We included randomised controlled trials (including crossover studies) and quasi-randomised trials comparing pharmacological treatments, and non-pharmacological treatments (vitamins and food supplements), and physical training in individuals with mitochondrial disorders. The primary outcome measures included an improvement in muscle strength and/or endurance, or neurological clinical features. Secondary outcome measures included quality of life assessments, biochemical markers of disease and negative outcomes.

Data collection and analysis

Details of the number of randomised patients, treatment, study design, study category, allocation concealment and patient characteristics were extracted. Analysis was based on intention to treat data. We planned to use meta-analysis, but this did not prove necessary.

Main results

Six hundred and seventy-eight abstracts were reviewed, and six fulfilled the entry criteria. Two trials studied the effects of co-enzyme Q10 (ubiquinone), one reporting a subjective improvement and a significant increase in a global scale of muscle strength, but the other trial did not show any benefit. Two trials used creatine, with one reporting improved measures of muscle strength and post-exercise lactate, but the other reported no benefit. One trial of dichloroacetate showed an improvement in secondary outcome measures of mitochondrial metabolism, and one trial using dimethylglycine showed no significant effect.

Authors' conclusions

There is currently no clear evidence supporting the use of any intervention in mitochondrial disorders. Further research is needed to establish the role of a wide range of therapeutic approaches.

 

Plain language summary

No clear evidence from randomised trials for the use of any intervention in mitochondrial disorders

There is currently no established treatment for mitochondrial disorders, a group of diseases particularly affecting muscles but also every other part of the body. They can cause progressive disability and premature death, due to the involvement of multiple organ systems. Dietary modifications, pharmacological agents and exercise therapy have been tried in individual cases and small cohorts. We identified six randomised controlled trials. Two trials studying co-enzyme Q10 and two studying creatine produced conflicting outcomes, one trial using dimethylglycine showed no positive effect, and one studying dichloroacetate improved some outcomes. Further randomised controlled trials of a range of therapies are needed.

 

摘要

背景

粒線體疾病的治療

粒線體呼吸鏈疾病是最普遍的遺傳性神經代謝疾病。其表現有中樞或周邊神經系統病變，也常合併其他器官受損，包括眼睛，心臟，肝臟，腎臟，糖尿病和感覺神經性耳聾。目前的治療大半是支持性療法，而疾病仍無情地進展，造成嚴重病狀和早期死亡。維生素補充劑，藥物治療和運動療法曾被用於個別病例及小規模臨床試驗，但這些治療的確切效果仍舊不明。

目標

確認是否有客觀的證據支持使用目前的療法，來治療線粒體疾病。

搜尋策略

查詢內容包括考科藍神經肌肉疾病臨床資料庫(2003年九月),考科藍中心資料庫, MEDLINE (1966年一月至2003年十月三日), EMBASE (1980年一月至2003年十月三日)及歐洲神經肌肉中心(ENMC) 的臨床實驗資料庫, 並聯絡本領域的專家.

選擇標準

選擇標準包括隨機對照試驗(含交叉研究)和準隨機試驗，比較藥物治療，非藥物治療(維生素和食品補充劑)，和體能訓練，對線粒體疾病的療效。初級成效包括肌力或耐力的改善，神經系統症狀的進步。次級成效包括生活品質的評估，疾病相關生化指標的檢查和有無造成不良的後果。

資料收集與分析

臨床實驗中擷取隨機的病人數目、治療、研究設計、研究類別、病人分配的隱匿性和病人的特徵等詳細數據。本分析是基於意向治療的結果。原本計劃是要用綜合分析的數據，但這種分析方式並沒有被證明是必要的

主要結論

總共檢閱了678篇文獻的摘要，其中6篇合於審查標準。有2個試驗在研究coenzyme Q10 (ubiquinone)的效果 ， 其中1篇報告顯示治療後患者主觀症狀的改善，和肌肉力量的顯著增加。但其他的試驗並沒有顯示有任何好處。另兩項試驗使用肌酸，其中之一顯示肌力及運動後乳酸的改善，但其他報導顯示的結果是毫無益處。還有一篇試驗了二氯乙酸的效果，結果顯示了治療後線粒體代謝的改善。至於使用dimethylglycine的試驗，則無顯著效果。

作者結論

目前有沒有明確的證據支持使用任何治療對粒腺體疾病有顯著療效。還需要進一步研究以確定這些治療方法的效果。

翻譯人

本摘要由新光醫院鍾禎智翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

從隨機試驗的結果中，沒有明確的證據提供粒腺體疾病的治療。目前也沒有確定的治療的方法。粒線體疾病由於影響範圍包括多器官系統，除了特別影響肌肉外，其他的身體部分也會受損，造成漸進式的殘疾和早期死亡。飲食控制、藥物和運動療法在一些病例報告和小型臨床試驗已經被嘗試過。本篇分析確認了6個隨機對照試驗。其中兩項試驗使用coenzyme Q10，另兩項實驗研究肌酸，這些實驗的結果卻是互相矛盾。另一試驗使用dimethylglycine顯示沒有任何效果。二氯乙酸的實驗有得到一些改善。這些療法的效用，還需要更進一步的隨機對照試驗才能確認。