Breath Test for Individualizing CD Therapy in Parkinson Disease

描述(申请人提供)：卡比多巴/左旋多巴(CD/LD)是帕金森病(PD)最有效的治疗方法，其疗效因患者而异。在开始治疗时，一些患者需要比其他患者更高的剂量才能达到同样的效果。还有一些人尽管服用了推荐剂量，但从未对CD/LD作出完全反应。随着疾病的发展，以反应质量降低和反应持续时间较短为特征的对CD/LD的不完全反应变得典型。有强有力的证据表明，LD的可用性可能是这些次优反应的部分原因。镉对LD的利用度有重要影响，因为它通过抑制外周LD脱羧基减少LD的外周分解，并允许更多的LD进入大脑，即临床作用的部位。因此，尝试个体化CD治疗可能被证明是帕金森病最重要的治疗策略。以前，由于无法获得安全、实用的技术来测量外周LD脱羧化的抑制程度，因此确定单个患者的最佳CD剂量的机会受到限制。物理科学公司(PSI)与其STTR合作伙伴波士顿VA Healthcare System和剑桥同位素实验室(CIL)合作，提议使用标记为LD的稳定同位素和13CO2呼气测试来确定个性化Cd剂量是否将改善PD的治疗。稳定同位素标记的LD没有放射性，因此对患者、研究人员或环境没有辐射风险。我们假设，针对每个患者的个体化CD治疗将比目前使用标准化CD/LD片剂的治疗方法有显著的改善。我们的初步数据表明，目前市售的CD/LD片剂中的CD剂量可能不足以满足许多PD患者的需求。拟议中的STTR项目的最终目标是开发一种简单的、基于办公室的呼气测试，可用于个性化和优化帕金森病的卡比多巴治疗。公共卫生相关性：这项拟议的研究旨在开发一种简单、安全和非侵入性的基于呼吸的分析方法，可供医生在卡比多巴/左旋多巴治疗帕金森病(PD)中个体化使用卡比多巴的最佳剂量。如果成功，这种新的药理探针可以帮助减少帕金森病患者中经常观察到的对卡比多巴/左旋多巴(SinemetTM)的可变反应，并增强这一非常重要的帕金森病疗法的益处。减少帕金森病患者“休息”时间的能力将是帕金森病治疗方法的重大进步。多达100万美国人患有帕金森病。据估计，70%到80%的接受治疗的帕金森病患者正在接受左旋多巴治疗。

DESCRIPTION (provided by applicant): Response to carbidopa/levodopa (CD/LD), the most efficacious therapy in Parkinson's disease (PD), is often variable among patients. At initiation of therapy, some patients require higher doses than others in order to achieve the same benefit. Still others never fully respond to CD/LD despite being on recommended doses. As the disorder progresses incomplete responses to CD/LD characterized by both a reduced quality of response as well as a shorter duration of response become typical. There is strong evidence to suggest that LD availability may, in part, be responsible for these sub optimal responses. CD has a critical impact on LD availability since it reduces the peripheral breakdown of LD by inhibiting peripheral LD decarboxylation and allows more LD to enter brain, the site of clinical action. Consequently, trying to individualize CD therapy could prove to be a most important therapeutic strategy for PD. The opportunity to determine the best CD dose for any individual patient was previously limited by the unavailability of safe, practical techniques to measure inhibition of peripheral LD decarboxylation. Physical Sciences Inc. (PSI) in collaboration with its STTR partner, Boston VA Healthcare System, and Cambridge Isotope Laboratories(CIL) proposes using stable isotope labeled LD and a 13CO2 breath test to determine if individualizing CD doses will improve treatment of PD. Stable isotope labeled LD is not radioactive and therefore presents no radiation risk to patients, investigators or environment. We hypothesize that individualizing CD therapy for each patient will provide for significant improvement over current therapy that uses standardized CD/LD tablets. Our preliminary data suggests that the current CD doses in commercially available CD/LD tablets may be inadequate for many PD patients. The ultimate goal of the proposed STTR project is to develop a simple, office-based breath test that can be used to individualize and optimize carbidopa therapy in Parkinson disease. PUBLIC HEALTH RELEVANCE: The proposed research seeks to develop a simple, safe and non-invasive breath-based assay that can be used by physicians to individualize the optimal dosing of carbidopa in carbidopa/levodopa therapy for Parkinson's disease (PD). If successful, this new pharmacologic probe could help reduce the variable response to carbidopa/levodopa (SinemetTM) that is often observed among PD patients and enhance the benefit of this very important PD therapy. The ability to diminish "off" time in PD would be a significant advance in the therapeutics of PD. As many as 1 million Americans suffer from PD. It is estimated that 70 to 80% of treated PD patients are on levodopa therapy.