{"title":"Catechol-O-methyl transferase (COMT) inhibitors in patients with Parkinson's disease: is COMT genotype a useful indicator of clinical efficacy?","authors":"Juha O Rinne, Ismo Ulmanen, Myung-Sik Lee","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>In clinical practice, two potent and selective catechol-O-methyl transferase (COMT) inhibitors are available for the control of motor fluctuation in patients with Parkinson's disease. However, because of the complexity of fluctuating motor symptoms, it is difficult to evaluate the clinical efficacy of COMT inhibitors in each individual. Therefore, an objective factor predicting the clinical efficacy of COMT inhibitors is needed. Individual variation in COMT activity is regulated by a single nucleotide of the COMT gene on the long arm of chromosome 22. Therefore, there could be a correlation between COMT genotype and the clinical efficacy of COMT inhibitors. Three double-blind studies evaluating the efficacy of a single or repeated doses of a COMT inhibitor failed to find significant difference in the improvement in the duration of daily 'on' time and degree of motor abilities between patients with different COMT genotypes. Furthermore, there were no significant differences in the severity and frequency of dopaminergic adverse effects between patients with different COMT genotypes. These data suggest that the COMT genotype is not a major factor in deciding the clinical efficacy of COMT inhibitors.</p>","PeriodicalId":72171,"journal":{"name":"American journal of pharmacogenomics : genomics-related research in drug development and clinical practice","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of pharmacogenomics : genomics-related research in drug development and clinical practice","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
In clinical practice, two potent and selective catechol-O-methyl transferase (COMT) inhibitors are available for the control of motor fluctuation in patients with Parkinson's disease. However, because of the complexity of fluctuating motor symptoms, it is difficult to evaluate the clinical efficacy of COMT inhibitors in each individual. Therefore, an objective factor predicting the clinical efficacy of COMT inhibitors is needed. Individual variation in COMT activity is regulated by a single nucleotide of the COMT gene on the long arm of chromosome 22. Therefore, there could be a correlation between COMT genotype and the clinical efficacy of COMT inhibitors. Three double-blind studies evaluating the efficacy of a single or repeated doses of a COMT inhibitor failed to find significant difference in the improvement in the duration of daily 'on' time and degree of motor abilities between patients with different COMT genotypes. Furthermore, there were no significant differences in the severity and frequency of dopaminergic adverse effects between patients with different COMT genotypes. These data suggest that the COMT genotype is not a major factor in deciding the clinical efficacy of COMT inhibitors.
儿茶酚- o -甲基转移酶(COMT)抑制剂在帕金森病患者中的应用:COMT基因型是临床疗效的有用指标吗?
在临床实践中,两种有效的选择性儿茶酚- o -甲基转移酶(COMT)抑制剂可用于控制帕金森病患者的运动波动。然而,由于波动运动症状的复杂性,很难评估COMT抑制剂在每个个体中的临床疗效。因此,需要一个客观的因素来预测COMT抑制剂的临床疗效。COMT活性的个体差异受22号染色体长臂上COMT基因的单个核苷酸的调控。因此,COMT基因型与COMT抑制剂的临床疗效可能存在相关性。三项评估单次或重复剂量COMT抑制剂疗效的双盲研究未能发现不同COMT基因型患者在每日服药时间和运动能力程度的改善方面存在显著差异。此外,不同COMT基因型患者多巴胺能不良反应的严重程度和频率无显著差异。这些数据表明,COMT基因型不是决定COMT抑制剂临床疗效的主要因素。