Treatment of Mitochondrial Disorders

Abstract

Opinion statement While numerous treatments for mitochondrial disorders have been suggested, relatively few have undergone controlled clinical trials. Treatment of these disorders is challenging, as only symptomatic therapy is available. In this review we will focus on newer drugs and treatment trials in mitochondrial diseases, with a special focus on medications to avoid in treating epilepsy and ICU patient with mitochondrial disease, which has not been included in such a review. Readers are also referred to the opinion statement in A Modern Approach to the Treatment of Mitochondrial Disease published in Current Treatment Options in Neurology 2009. Many of the supplements used for treatment were reviewed in the previous abstract, and dosing guidelines were provided. The focus of this review is on items not previously covered in depth, and our discussion includes more recently studied compounds as well as any relevant updates on older compounds. We review a variety of vitamins and xenobiotics, including dichloroacetate (DCA), arginine, coenzyme Q10, idebenone, EPI-743, and exercise training. Treatment of epilepsy, which is a common feature in many mitochondrial phenotypes, warrants special consideration due to the added toxicity of certain medications, and we provide a discussion of these unique treatment challenges. Interesting, however, with only a few exceptions, the treatment strategies for epilepsy in mitochondrial cytopathies are the same as for epilepsy without mitochondrial dysfunction. We also discuss intensive care management, building upon similar reviews, adding new dimensions, and demonstrating the complexity of overall care of these patients.

Mitochonic Acid 5 (MA-5), a Derivative of the Plant Hormone Indole-3-Acetic Acid, Improves Survival of Fibroblasts from Patients with Mitochondrial Diseases

“…Antioxidant quinones (e.g. coenzyme Q10 (CoQ10), idebenone) have been used clinically to prevent the disease progression (Avula et al 2014;Enns 2014), but the effectiveness of such quinones has not been well established (Pfeffer et al 2012). Therefore, an alternative effective therapeutic approach is still urgently needed.…”

Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment

“…While discussion of each agent's detailed mechanism of action in PMD/SMD is beyond the scope of this review, we have highlighted the most commonly used ubiquinone (CoQ10) and provided examples of some combination therapies. Even though Pfeffer et al [2012] concluded that there is no clear evidence supporting any interventions in mitochondrial disorders, more promising trials have been conducted recently and are currently in process [Kerr, 2013;Avula et al, 2014;Enns, 2014;Tischner and Wenz, 2015].…”

Recognition, investigation and management of mitochondrial disease

“…Certain drugs have the potential to be detrimental in the context of a mitochondrial disorder and should be avoided or used with caution 40. These include sodium valproate (risk of hepatotoxicity, and contraindicated in patients with POLG mutations) and anaesthetic agents such as propofol 41…”