The effect of short-term dimethylglycine treatment on oxygen consumption in cytochrome oxidase deficiency: A double-blind randomized crossover clinical trial

Therapeutic Strategies for Mitochondrial Disorders

“…No significant side effects were observed. 61 Induction of vasoactive effects. This approach is applied only to patients who experience stroke-like episodes.…”

“…28 In a randomized, double-blind placebo-controlled crossover trial in five children with cytochrome-c-oxidase deficiency, dimethylglycine did not show a beneficial effect. 61 Depending on their body weight, the included children received 50 mg/kg/ day or 5 g/day dimethylglycine, and the outcome variables were serum lactate, pyruvate, bicarbonate, pH, and VO2. 61 The drug did not exhibit any detectable effect on serum lactate, pyruvate, bicarbonate, or pH.…”

“…61 Depending on their body weight, the included children received 50 mg/kg/ day or 5 g/day dimethylglycine, and the outcome variables were serum lactate, pyruvate, bicarbonate, pH, and VO2. 61 The drug did not exhibit any detectable effect on serum lactate, pyruvate, bicarbonate, or pH. No significant side effects were observed.…”

Why are there no proven therapies for genetic mitochondrial diseases?

“…Forty-three (57%) of these published trials were randomized controlled trials (RCTs) that were double-blinded and most compared active treatment to placebo. However, only 10 of the RCTs (13%), representing 7×10 −5 % of all citations, were conducted in patients with congenital causes of mitochondrial disease due to proven enzymatic and/or molecular genetic defects in the pyruvate dehydrogenase complex (PDC) or in one or more respiratory chain complexes or in subjects with histological or immunochemical criteria consistent with “mitochondrial cytopathy.” All studies were single-center trials that evaluated dichloroacetate (DCA; 3 studies) (Duncan et al 2004; Kaufmann et al 2006; Stacpoole et al 2006), a naturally occurring molecule (vitamin, cofactor or food; 5 studies) (Glover et al 2010; Klopstock et al 2000; Kornblum et al 2005; Liet et al 2003; Tarnopolsky et al 1997) or a mixture of nutraceuticals (1 study) (Rodriguez et al 2007). Five trials reported a positive effect of treatment on one or more clinical or biochemical primary endpoints (Duncan et al 2004; Glover et al 2010; Rodriguez et al 2007; Stacpoole et al 2006; Tarnopolsky et al 1997).…”

How Can We Treat Mitochondrial Encephalomyopathies? Approaches to Therapy

“…17 There was objective evidence of locomotor functional improvement with CoQ10 and creatine monohydrate, but with conflicting data for both agents. The trials showed no effect when using higher doses of the oral agent, ruling out inadequate dosage as an explanation for the resultant lack of response.…”