DICHLOROACETATE IN MITOCHONDRIAL DISEASE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。二氯乙酸酯(DCA)似乎对患有线粒体电子传递链缺陷的患者有一些有益的影响。这种药物通过刺激丙酮酸脱氢酶复合酶的活性而起作用。这种酶的刺激导致丙酮酸向乙酰辅酶A的代谢增加，从而远离乳酸的产生。因此，据推测，这种药物将使患有线粒体细胞病变等导致乳酸水平升高的患者受益。虽然这种药物的临床应用有限，但已经确定了某些副作用。其中包括血糖代谢的改变，从而可能导致低血糖。神经传导速度的改变也有报道。这种药物的降血糖作用在治疗的最初阶段似乎更加突出，因此，患者在医院受到密切监测，并经常进行血糖评估。还建议在此治疗开始前记录神经传导速度，并在治疗后定期记录。据报道，对神经传导的影响与剂量有关，神经传导速度的降低将需要降低甚至可能停止这种治疗。患者将定期接受神经学检查和神经传导研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dichloroacetate (DCA) appears to have some beneficial effect in patients with mitochondrial electron transport chain defects. This medication acts by stimulating the activity of the pyruvate dehydrogenase complex enzyme. The stimulation of this enzyme results in increased metabolism of pyruvate to acetyl CoA and away from lactate production. As such, it has been postulated that this medication would benefit patients with conditions such as mitochondrial cytopathies that result in elevated lactate levels. Although the clinical use of this medication has been limited, certain side effects have been identified. These have included an alteration of blood glucose metabolism such that hypoglycemia may result. Alterations in nerve conduction velocity have also been reported. The hypoglycemia effects of this drug appear to be more prominent in the initial phases of treatment and for this reason patients are monitored closely in the hospital setting with frequent blood glucose evaluations. it is also recommended that nerve conduction velocities be documented prior to the onset of this treatment and at regular intervals thereafter. The effect on nerve conduction is reportedly dose-related and a reduction in nerve conduction velocity would necessitate a decrease and possibly a cessation of this therapy. The patient will be followed at regular intervals with neurological examinations and nerve conduction studies.