DICHLOROACETATE IN MITOCHONDRIAL DISEASE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。二氯乙酸（DCA）似乎对线粒体电子传递链缺陷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起作用。这种酶的刺激导致丙酮酸代谢为乙酰辅酶A的增加，并远离乳酸的产生。因此，据推测，这种药物将有利于患者的条件，如线粒体细胞病变，导致乳酸水平升高。 虽然这种药物的临床使用受到限制，但已发现某些副作用。这些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。这种药物的低血糖效应在治疗的初始阶段似乎更突出，因此，在医院环境中密切监测患者，并频繁进行血糖评价。还建议在治疗开始之前和之后定期记录神经传导速度。据报告，对神经传导的影响与剂量相关，神经传导速度降低将需要减少并可能停止该治疗。 将定期对患者进行神经系统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.