Dichloroacetate treatment for mitochondrial cytopathy: long-term effects in MELAS

被引:32
作者
Mori, M [1 ]
Yamagata, T [1 ]
Goto, T [1 ]
Saito, S [1 ]
Momoi, MY [1 ]
机构
[1] Jichi Med Sch, Dept Pediat, Minami Kawachi, Tochigi 3290498, Japan
关键词
mitochondrial encephalomyelopathy with lactic acidosis and stroke-like episodes; treatment; dichloroacetate; long-term effects;
D O I
10.1016/j.braindev.2003.12.009
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The long-term effects of the sodium salt of dichloroacetic acid (DCA) were evaluated in four patients with mitochondrial encephalomyelopathy with lactic acidosis and stroke-like episodes (MELAS) carrying A3243G mutation. Oral administration of DCA in MELAS patients was followed for an average of 5 years 4 months. Serum levels of lactate and pyruvate were maintained at around 10 and 0.6 mg/dl, respectively. Serum levels of DCA were 40-136 pLg/ml. Symptoms responding to treatment included persistent headache, abdominal pain, muscle weakness, and stroke-like episodes. In contrast, no improvements in mental status, deafness, short stature, or neuroelectrophysiological findings were observed. Adverse effects included mild liver dysfunction in all patients, hypocalcemia in three and peripheral neuropathy in one. None of these adverse events was severe enough to require discontinuation of treatment. To determine suitable indications for DCA therapy, analysis of many more patients who have undergone DCA administration is required. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:453 / 458
页数:6
相关论文
共 32 条
[21]   THERAPEUTIC EFFECT OF SODIUM DICHLOROACETATE ON VISUAL AND AUDITORY HALLUCINATIONS IN A PATIENT WITH MELAS [J].
SAIJO, T ;
NAITO, E ;
ITO, M ;
TAKEDA, E ;
HASHIMOTO, T ;
KURODA, Y .
NEUROPEDIATRICS, 1991, 22 (03) :166-167
[22]   Effects of dichloroacetate in three patients with MELAS [J].
Saitoh, S ;
Momoi, MY ;
Yamagata, T ;
Mori, Y ;
Imai, M .
NEUROLOGY, 1998, 50 (02) :531-534
[23]   DICHLOROACETATE IN THE TREATMENT OF LACTIC-ACIDOSIS [J].
STACPOOLE, PW ;
LORENZ, AC ;
THOMAS, RG ;
HARMAN, EM .
ANNALS OF INTERNAL MEDICINE, 1988, 108 (01) :58-63
[24]   A CONTROLLED CLINICAL-TRIAL OF DICHLOROACETATE FOR TREATMENT OF LACTIC-ACIDOSIS IN ADULTS [J].
STACPOOLE, PW ;
WRIGHT, EC ;
BAUMGARTNER, TG ;
BERSIN, RM ;
BUCHALTER, S ;
CURRY, SH ;
DUNCAN, CA ;
HARMAN, EM ;
HENDERSON, GN ;
JENKINSON, S ;
LACHIN, JM ;
LORENZ, A ;
SCHNEIDER, SH ;
SIEGEL, JH ;
SUMMER, WR ;
THOMPSON, D ;
WOLFE, CL ;
ZOROVICH, B .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 327 (22) :1564-1569
[25]   DICHLOROACETATE [J].
STACPOOLE, PW ;
GREENE, YJ .
DIABETES CARE, 1992, 15 (06) :785-791
[26]   Clinical pharmacology and toxicology of dichloroacetate [J].
Stacpoole, PW ;
Henderson, GN ;
Yan, ZM ;
James, MO .
ENVIRONMENTAL HEALTH PERSPECTIVES, 1998, 106 :989-994
[27]   Dichloroacetate treatment in leigh syndrome caused by mitochondrial DNA mutation [J].
Takanashi, J ;
Sugita, K ;
Tanabe, Y ;
Maemoto, T ;
Niimi, H .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1997, 145 (01) :83-86
[28]   Treatment of mitochondrial encephalomyopathy with a combination of cytochrome C and vitamins B-1 and B-2 [J].
Tanaka, J ;
Nagai, T ;
Arai, H ;
Inui, K ;
Yamanouchi, H ;
Goto, Y ;
Nonaka, I ;
Okada, S .
BRAIN & DEVELOPMENT, 1997, 19 (04) :262-267
[29]   Dichloroacetate improves cardiac efficiency after ischemia independent of changes in mitochondrial proton leak [J].
Taniguchi, M ;
Wilson, C ;
Hunter, CA ;
Pehowich, DJ ;
Clanachan, AS ;
Lopaschuk, GD .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2001, 280 (04) :H1762-H1769
[30]   TRANSIENT IMPROVEMENT OF CONGENITAL LACTIC-ACIDOSIS IN A MALE INFANT WITH PYRUVATE DECARBOXYLASE DEFICIENCY TREATED WITH DICHLOROACETATE [J].
TOTH, PP ;
ELSHANTI, H ;
EIVINS, S ;
RHEAD, WJ ;
KLEIN, JM .
JOURNAL OF PEDIATRICS, 1993, 123 (03) :427-430