Concomitant administration of sodium dichloroacetate and vitamin B1 for lactic acidemia in children with MELAS syndrome

Kuroda, Yasuhiro; M, Ito; Naito, Etsuo; Yokota, Ichiro; Matsuda, Junko; Saijo, Takahiko; Kondo, Shuji; Yoneda, Yoshihiro; Miyazaki, Masahito; Mori, Koichi; Iwamoto, Hiroko

doi:10.1016/s0022-3476(97)80075-3

Cited by 21 publications

(6 citation statements)

References 12 publications

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“…Keeping PDH in the dephosphorylated, active form favors pyruvate metabolism and decreases lactate concentration 16. There is anecdotal evidence of clinical improvement in children with mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS),17–21 but the first double‐blind, placebo‐controlled trial in a large cohort of MELAS patients is still underway in our center. One serious disadvantage of dichloroacetate is that it often causes or exacerbates peripheral neuropathy, even when it is administered together with thiamine (8.6 mg/kg).…”

Section: Removal Of Noxious Metabolitesmentioning

confidence: 99%

Mitochondrial Encephalomyopathies: Therapeutic Approach

DiMauro

Mancuso

Naini

2004

Annals of the New York Academy of Sciences

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Therapy for mitochondrial diseases is woefully inadequate. How-ever, lack of cure does not equate with lack of treatment. In this review, we consider sequentially several different therapeutic approaches. Palliative therapy is dictated by good medical practice and includes anticonvulsant medication, control of endocrine dysfunction, and surgical procedures. Removal of noxious metabolites is centered on combating lactic acidosis, but it extends to other metabolites, such as thymidine in patients with the mitochondrial neurogastrointestinal encephalomyopathy syndrome. Attempts to bypass blocks in the respiratory chain by administration of artificial electron acceptors have not been successful, but this concept may be amenable to genetic engineering. Administration of metabolites and cofactors is the mainstay of real-life therapy and includes both components of the respiratory chain and other natural compounds. There is increasing interest in the administration of reactive oxygen species scavengers both in primary mitochondrial diseases and in neurodegenerative diseases directly or indirectly related to mitochondrial dysfunction. Aerobic exercise and physical therapy prevent or correct deconditioning and improve exercise tolerance in patients with mitochondrial myopathies due to mtDNA mutations. Gene therapy is a challenge because of polyplasmy and heteroplasmy, but interesting experimental approaches are being pursued and include, for example, decreasing the ratio of mutant to wild-type mitochondrial genomes (gene shifting), converting mutated mtDNA genes into normal nDNA genes (allotropic expression), importing cognate genes from other species, or correcting mtDNA mutations with specific restriction endonucleases. Germline therapy raises ethical problems but is being seriously considered to prevent maternal transmission of mtDNA mutations. Preventive therapy through genetic counseling and prenatal diagnosis is still limited for mtDNA-related disorders but is becoming increasingly important for nDNA-related disorders.

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Section: Removal Of Noxious Metabolitesmentioning

confidence: 99%

Mitochondrial Encephalomyopathies: Therapeutic Approach

DiMauro

Mancuso

Naini

2004

Annals of the New York Academy of Sciences

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“…[ 19 – 21 ] However, several case reports using a “cocktail” of supplements have shown clinical and biochemical improvements after treatment. [ 22 – 24 ] For pulmonary hypertension complicated with mitochondrial disorder, rare relevant treatment research has been reported. In our case, the target therapy of pulmonary hypertension was ineffective.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary hypertension as a manifestation of mitochondrial disease

Xu¹,

Xu²,

Zhang³

et al. 2017

Medicine

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Background:Mitochondrial diseases are a group of multisystem heterogeneous diseases caused by pathologic dysfunction of the mitochondrial respiratory chain. A wide range of clinical expression has been described. However, pulmonary hypertension has rarely been described in association with mitochondrial disease until the past decade, and there is no currently recognized treatment for the pulmonary hypertension complicated with mitochondrial disorder.Patient concerns:We reported the case of a 15-year-old boy who presented with shortness of breath and exercise limitation after a cold, and the diagnosis of pulmonary hypertension was confirmed by right heart catheter. Other examinations, such as blood tests, high- resolution chest computed tomography scan, and pulmonary function test, excluded other associated diseases as causes of pulmonary hypertension.Diagnoses and Outcomes:The initial diagnosis was idiopathic pulmonary arterial hypertension and an injection of vasodilator (Treprostinil) was given. However, the dyspnea and fatigue subsequently got worsened. Tracing back his family history, together with the electromyography, nerve conduction studies, and the result of muscle biopsy, mitochondrial disease was confirmed. After treatment with vitamin E, vitamin B2, ATP, and coenzyme Q10, the patient's condition improved.Conclusion:Pulmonary hypertension should be considered as another potential manifestation of mitochondrial disease. Both mechanism and treatment for pulmonary hypertension complicated with mitochondrial disease are unclear. Further study is necessary.

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“…DCA inhibits the phosphorylation of pyruvate dehydrogenase (PDH), thereby keeping the enzyme in the dephosphorylated, active state [19]. There is anecdotal evidence that DCA improves the clinical outcome in children with MELAS (increased growth, reduced frequency of stroke-like episodes) [20][21][22][23] and in COX deficiency [24]. One drawback of DCA is that it may cause peripheral neuropathy unless it is administered together with thiamine [25,26].…”

Section: Removal Of Toxic Metabolitesmentioning

confidence: 99%

Medicinal and Genetic Approaches to the Treatment of Mitochondrial Disease

Schon

DiMauro²

2003

Current Medicinal Chemistry

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Although great progress has been made in our understanding of the molecular bases of mitochondrial disorders due to defects in the respiratory chain, little exists in the way of rational therapy. Possible therapeutic approaches include: palliative therapy; removal of noxious metabolites; administration of artificial electron acceptors, metabolites, and free radical scavengers; genetic counseling; and gene therapy. There has been progress with each of these approaches, although much work remains to be done. Finally, a novel approach to treating a specific mitochondrial disorder, MELAS, is presented.

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Concomitant administration of sodium dichloroacetate and vitamin B1 for lactic acidemia in children with MELAS syndrome

Cited by 21 publications

References 12 publications

Mitochondrial Encephalomyopathies: Therapeutic Approach

Mitochondrial Encephalomyopathies: Therapeutic Approach

Pulmonary hypertension as a manifestation of mitochondrial disease

Medicinal and Genetic Approaches to the Treatment of Mitochondrial Disease

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