Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial

Ohsawa, Yutaka; Hagiwara, Hiroki; Nishimatsu, Shin‐ichiro; Hirakawa, Akihiro; Kamimura, Naomi; Ohtsubo, Hideaki; Fukai, Yuta; Murakami, Tatsufumi; Koga, Yasutoshi; Goto, Yu‐ichi; Ohta, Shigeo; Sunada, Yoshihide

doi:10.1136/jnnp-2018-317964

Cited by 97 publications

(62 citation statements)

References 25 publications

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“…More in general, it might be worth investigating the potential of ccf-mtDNA in monitoring, by longitudinal follow-up assessments, natural history of mitochondrial diseases, and therapy response, including both therapies aimed at contrasting the disease etiology, as well as the potential benefit of anti-inflammatory therapies. In particular for MELAS, ccf-mtDNA represents a promising biomarker in evaluating the efficacy of recently proposed therapies aimed at preventing SLEs, such as arginine, citrulline, and taurine supplementation [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Expanding and validating the biomarkers for mitochondrial diseases

et al. 2020

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Mitochondrial diseases are highly heterogeneous metabolic disorders caused by genetic alterations in the mitochondrial DNA (mtDNA) or in the nuclear genome. In this study, we investigated a panel of blood biomarkers in a cohort of 123 mitochondrial patients, with prominent neurological and muscular manifestations. These biomarkers included creatine, fibroblast growth factor 21 (FGF21) and growth/differentiation factor 15 (GDF-15), and the novel cell free circulating-mtDNA (ccf-mtDNA). All biomarkers were significantly increased in the patient group. After stratification by the specific phenotypes, ccf-mtDNA was significantly increased in the Mitochondrial Encephalomyopathy Lactic Acidosis Stroke-like episodes syndrome (MELAS) group, and FGF21 and GDF-15 were significantly elevated in patients with MELAS and Myoclonic Epilepsy Ragged Red Fibers syndrome. On the contrary, in our cohort, creatine was not associated to a specific clinical phenotype. Longitudinal assessment in four MELAS patients showed increased levels of ccf-mtDNA in relation to acute events (stroke-like episodes/status epilepticus) or progression of neurodegeneration. Our results confirm the association of FGF21 and GDF-15 with mitochondrial translation defects due to tRNA mutations. Most notably, the novel ccf-mtDNA was strongly associated with MELAS and may be used for monitoring the disease course or to evaluate the efficacy of therapies, especially in the acute phase. Key messages • FGF21/GDF15 efficiently identifies mitochondrial diseases due to mutations in tRNA genes. • The novel ccf-mtDNA is associated with MELAS and increases during acute events. • Creatine only discriminates severe mitochondrial patients. • FGF21, GDF-15, and ccf-mtDNA are possibly useful for monitoring therapy efficacy.

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Section: Discussionmentioning

confidence: 99%

Expanding and validating the biomarkers for mitochondrial diseases

et al. 2020

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“…On the other hand, very few drugs for the treatment of mitochondrial diseases have been approved to date. In Europe, only Raxone (Idebenone) is approved for Leber's hereditary optic neuropathy (LHON) 27,28 , and in Japan, Taurine is approved for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) 29 . Idebenone, taurine and most therapeutic candidates are small molecule drugs that attempt to temporarily improve mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Validation of a mitochondrial RNA therapeutic strategy using fibroblasts from a Leigh syndrome patient with a mutation in the mitochondrial ND3 gene

Yamada

Somiya

Miyauchi

et al. 2020

Sci Rep

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We report on the validation of a mitochondrial gene therapeutic strategy using fibroblasts from a Leigh syndrome patient by the mitochondrial delivery of therapeutic mRNA. The treatment involves delivering normal ND3 protein-encoding mRNA as a therapeutic RNA to mitochondria of the fibroblasts from a patient with a T10158C mutation in the mtDNA coding the ND3 protein, a component of the mitochondrial respiratory chain complex I. The treatment involved the use of a liposome-based carrier (a MITO-Porter) for delivering therapeutic RNA to mitochondria via membrane fusion. The results confirmed that the mitochondrial transfection of therapeutic RNA by the MITO-Porter system resulted in a decrease in the levels of mutant RNA in mitochondria of diseased cells based on reverse transcription quantitative PCR. An evaluation of mitochondrial respiratory activity by respirometry also showed that transfection using the MITO-Porter resulted in an increase in maximal mitochondrial respiratory activity in the diseased cells.

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“…In addition, oral administration of 2 g taurine/day for 4 weeks resulted in clinically significant reductions in the frequency, duration, and intensity of muscle cramps in patients with chronic liver disease (Vidot et al 2018). Furthermore, long-term oral administration of taurine (9 or 12 g per day) for 52 weeks can effectively reduce the recurrence of stroke-like episodes in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), a rare genetic disorder caused by point mutations in the mitochondrial DNA (Ohsawa et al 2019). These beneficial effects of oral taurine are summarized in Table 2.…”

Section: Health Benefits Of Taurine Supplementationmentioning

confidence: 99%

Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health

2020

Amino Acids

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Taurine (a sulfur-containing β-amino acid), creatine (a metabolite of arginine, glycine and methionine), carnosine (a dipeptide; β-alanyl-l-histidine), and 4-hydroxyproline (an imino acid; also often referred to as an amino acid) were discovered in cattle, and the discovery of anserine (a methylated product of carnosine; β-alanyl-1-methyl-l-histidine) also originated with cattle. These five nutrients are highly abundant in beef, and have important physiological roles in anti-oxidative and antiinflammatory reactions, as well as neurological, muscular, retinal, immunological and cardiovascular function. Of particular note, taurine, carnosine, anserine, and creatine are absent from plants, and hydroxyproline is negligible in many plant-source foods. Consumption of 30 g dry beef can fully meet daily physiological needs of the healthy 70-kg adult human for taurine and carnosine, and can also provide large amounts of creatine, anserine and 4-hydroxyproline to improve human nutrition and health, including metabolic, retinal, immunological, muscular, cartilage, neurological, and cardiovascular health. The present review provides the public with the much-needed knowledge of nutritionally and physiologically significant amino acids, dipeptides and creatine in animal-source foods (including beef). Dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline are beneficial for preventing and treating obesity, cardiovascular dysfunction, and ageing-related disorders, as well as inhibiting tumorigenesis, improving skin and bone health, ameliorating neurological abnormalities, and promoting well being in infants, children and adults. Furthermore, these nutrients may promote the immunological defense of humans against infections by bacteria, fungi, parasites, and viruses (including coronavirus) through enhancing the metabolism and functions of monocytes, macrophages, and other cells of the immune system. Red meat (including beef) is a functional food for optimizing human growth, development and health.

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Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial

Cited by 97 publications

References 25 publications

Expanding and validating the biomarkers for mitochondrial diseases

Expanding and validating the biomarkers for mitochondrial diseases

Validation of a mitochondrial RNA therapeutic strategy using fibroblasts from a Leigh syndrome patient with a mutation in the mitochondrial ND3 gene

Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health

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