Breath Test for Individualizing CD Therapy in Parkinson Disease

描述（由申请人提供）：卡比多巴/左旋多巴（CD/LD）是帕金森病（PD）最有效的治疗方法，但患者对卡比多巴/左旋多巴的反应往往是不同的。在治疗开始时，一些患者需要比其他患者更高的剂量，以达到同样的效果。还有一些人尽管服用了推荐剂量，但对CD/LD没有完全反应。随着疾病的进展，以反应质量降低和反应持续时间缩短为特征的CD/LD不完全反应成为典型。有强有力的证据表明，LD可用性可能在一定程度上导致了这些次优响应。CD对LD的有效性有关键影响，因为它通过抑制外周LD脱羧减少LD的外周分解，并允许更多的LD进入大脑，这是临床作用的部位。因此，尝试个体化乳糜泻治疗可能被证明是PD最重要的治疗策略。以前，由于没有安全实用的技术来测量外周LD脱羧抑制作用，确定任何个体患者的最佳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医疗保健系统和剑桥同位素实验室（CIL）合作，建议使用稳定同位素标记的LD和13CO2呼吸测试来确定个体化CD剂量是否会改善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。我们假设针对每位患者的个体化乳糜泻治疗将比目前使用标准化乳糜泻/LD片剂的治疗提供显著的改善。我们的初步数据表明，目前市售的CD/LD片剂中的CD剂量可能不适合许多PD患者。拟议的STTR项目的最终目标是开发一种简单的，基于办公室的呼吸测试，可用于个性化和优化卡比多巴治疗帕金森病。公共卫生相关性：拟议的研究旨在开发一种简单、安全、无创的基于呼吸的检测方法，可用于医生在卡比多巴/左旋多巴治疗帕金森病（PD）时个体化卡比多巴的最佳剂量。如果成功，这种新的药理学探针将有助于减少PD患者对卡比多巴/左旋多巴（SinemetTM）的可变反应，并增强这种非常重要的PD治疗的益处。减少帕金森病“关闭”时间的能力将是帕金森病治疗的重大进步。多达100万美国人患有帕金森病。据估计，70%至80%的PD患者接受左旋多巴治疗。

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.