Istradefylline

Bringing medical advances from the lab to the clinic. （点击👆，免费获取美国NIH基金资助项目大数据分析） 帕金森病（Parkinson’s Disease, PD） 是一种常见的中枢神经系统变性疾病，主要由于中脑黑质多巴胺能神经元逐渐丧失及路易小体异常聚集所致。其核心症状包括运动迟缓、震颤、肌强直和姿势平衡障碍，同时常伴有睡眠障碍、抑郁、认知功能下降等非运动症状。帕金森病发病隐匿、进展缓慢，严重影响患者生活质量。 最新研究进展 病理机制新认识：研究证实，α-突触核蛋白异常聚集是疾病关键环节，肠-脑轴、线粒体功能障碍及神经炎症反应被认为在发病中起重要作用。 早期诊断与生物标志物探索：外周体液中α-突触核蛋白、神经丝轻链蛋白及影像学（如多巴胺转运体显像）为早期诊断提供潜在工具。 药物治疗进展：除传统左旋多巴外，多巴胺受体激动剂、MAO-B抑制剂及腺苷A2A受体拮抗剂（如istradefylline）已被用于多阶段治疗；针对α-突触核蛋白的免疫治疗和基因疗法正在临床试验中。 脑深部刺激（DBS）与神经调控技术：DBS已成为晚期患者运动症状控制的重要手段，新一代闭环刺激系统可实时调节刺激参数以提高疗效。 再生医学与细胞治疗：诱导多能干细胞（iPSC）来源的多巴胺神经元移植在动物及早期临床研究中显示出功能改善潜力。 亟需解决的临床痛点 早期诊断困难：缺乏高特异性生物标志物，患者常在神经元损失过半后才确诊。 疾病修饰性治疗缺乏：目前药物主要缓解症状，无法阻止神经退行性进展。 长期用药并发症：长期左旋多巴治疗可导致运动波动和异动症。 非运动症状管理不足：抑郁、认知障碍和自主神经功能紊乱常被忽视。 个体化治疗与长期管理挑战：不同患者的病程、症状与药物反应差异大，亟需精准化管理方案。 帕金森病的研究正从传统的对症治疗迈向机制导向的精准干预阶段。未来的重点在于早期诊断标志物的验证、疾病修饰性疗法的研发，以及整合药物、神经调控与再生医学的综合治疗策略，以实现延缓病程和改善生活质量的目标。 我们仅对美国国立卫生研究院（NIH）资助的在研帕金森相关项目进行梳理，希望给同仁们的选题思路提供一点启发。 2025年，以 "Parkinson’s Disease"为检索词、在题目中进行检索，美国NIH针对帕金森的在研有197项。 一，谁获得了这些研究？ 1. 在研基金最多的PI： CORCOS, DANIEL M.，芝加哥西北大学（NORTHWESTERN UNIVERSITY AT CHICAGO） PERLMUTTER, JOEL SYNES，华盛顿大学（WASHINGTON UNIVERSITY） ALBIN, ROGER L，密歇根大学安娜堡分校（UNIVERSITY OF MICHIGAN AT ANN ARBOR） 2，基金最多的研究机构 NORTHWESTERN UNIVERSITY AT CHICAGO  芝加哥西北大学 WASHINGTON UNIVERSITY  华盛顿大学（圣路易斯） UNIVERSITY OF MICHIGAN AT ANN ARBOR  密歇根大学安娜堡分校 UNIVERSITY OF PENNSYLVANIA  宾夕法尼亚大学 UNIVERSITY OF IOWA  爱荷华大学 二，研究热点 研究领域总览（根据关键词） 研究大的方向也包括PDL1、PD患者、T细胞（T Cells）、认知障碍（Cognitive Impairment）、临床试验（Clinical Trails）、长期（Long Term）等。 三，借鉴与突破 我们也分享在美国该领域的几项课题摘要，希望对同仁们有所启发。 A，Disparities in REsults of Immune Checkpoint Inhibitor Treatment (DiRECT): A Prospective Cohort Study of Cancer Survivors Treated with anti-PD-1/anti-PD-L1 in a Community Oncology Setting Immune checkpoint inhibitors (ICIs) are a powerful and innovative mode of cancer therapy, believed to be partially responsible for the largest single-year drop in cancer mortality from 2016 to 2017. Their use has increased dramatically over the past 3 years. However, little data has been collected about ICI treatment response among patients of African ancestry (AA). In addition, little is known about the toxicities, treatment patterns, long-term outcomes, and post-treatment quality of life associated with ICIs outside the clinical trials setting. A prospective cohort study with a focus on racial differences between AA patients and patients of European ancestry (EA) in community oncology settings could address these knowledge gaps. Focusing on racial differences in ICI impact is important for three reasons. First, at the population level, AA patients are more likely than EA patients to have advanced cancers, an important disease group ICIs are intended to treat. Second, due to racial differences in host immunity, AA individuals tend to have a stronger pro-inflammatory response than EAs. This could lead to a higher risk of immune-related adverse events (irAEs) while on ICIs. Third, as a result of immune differences, AA patients who manage irAEs and continue ICI treatment may be more likely to benefit than EA patients. However, AA populations may experience multiple barriers while accessing healthcare (e.g., discrimination, financial toxicity) that may lead to discontinuing ICIs. We have a unique opportunity to assess the treatment, disease, individual, lifestyle, and quality of life factors that contribute to differential experiences of AA patients on ICIs, by accruing a prospective cohort through the nationwide NCI Community Oncology Research Program (NCORP) network. We will include all patients receiving anti-PD-1/-L1 therapy regardless of cancer site and enroll a total of 600 AA and 1,200 EA patients, with 1:2 match of AA to EA patients on cancer type within NCORP site. Our Specific Aims are: 1. To examine racial differences and predictors of irAEs, comparing AA and EA patients on incidence and severity of irAEs and assessing disease, individual, and lifestyle factors as predictors of these differences. 2. To examine treatment delay and discontinuation between AA and EA patients and assess racial differences in irAEs, healthcare barriers, and other factors as potential causes of treatment interruptions. 3. To examine short- and long-term treatment outcomes, comparing AA and EA patients on objective response rate (ORR), recurrence, death, and HRQOL after ICIs, and assessing treatment, disease, individual, and lifestyle factors as predictors of patient outcomes and potential causes of racial differences. We envision this to be the first large cohort study of diverse AA and EA patients treated with ICIs. We will gain valuable knowledge of the usage, effects, and challenges of ICIs in community oncology settings. Our findings may inform use of ICIs, management of irAEs and reduction of healthcare barriers across populations. B, Study in Parkinson Disease of Exercise Phase 3 Clinical Trial: SPARX3 The study objective is to establish the efficacy of high-intensity endurance exercise as first-line therapy for recently diagnosed people with Parkinson's disease (PD). No medications are yet proven to slow the progression of the signs of PD and dopaminergic medications do not benefit all the signs of PD. As such, people with PD have no adequate treatment to slow down the progression of the motor or non-motor signs of the disease. The key question is whether there is an additional benefit of exercising at high-intensity, in terms of slowing the progression of the signs of the disease, beyond the well documented benefit of treadmill training on general parameters of fitness, gait and functional mobility. Preclinical data, experimental data on humans, and epidemiological data all have demonstrated benefits of endurance exercise on the motor and nonmotor signs and symptoms of the disease, although the best dose for slowing down their progression has not been identified. We recently completed a multicenter Phase II clinical trial, the SPARX study, using a futility design. We studied the feasibility of participants with PD performing moderate intensity (60-65% of their maximal heart rate (HRmax)) and high intensity endurance exercise (80-85% HRmax). Participants had not yet started dopaminergic medication. We demonstrated that: 1) participants will exercise at between 80-85% of HRmax for at least 6 months, 2) they will exercise for at least 3 days per week, 3) adverse events are low, and 4) exercising at 80- 85% HRmax slowed progression by 2.9 points on the motor section of the UPDRS when compared to the wait list usual care group and was not deemed futile. These 4 findings were deemed a priori to be the necessary results to proceed to a Phase III efficacy trial. We now propose to conduct a 12-month multi-center, randomized (two doses of intensity), evaluator-masked study of high intensity endurance exercise. The 2 doses of treadmill exercise are moderate intensity (4 days/wk for 30 minutes per session at 60- 65% HRmax) and high intensity (4 days/wk for 30 minutes per session at 80-85% HRmax). The study is designed to test 3 specific aims. First, to establish the efficacy of high-intensity endurance exercise to slow the progression of the signs of PD as measured by the change in the MDS-Unified Parkinson Disease Rating Scale (MDS-UPDRS Part III) score over 6 and 12 months. Second, to ascertain the effect of high dose endurance versus moderate dose endurance exercise on the progression of the signs of PD over 6 and 12 months as measured by: 1) distance covered in 6 minute walk, 2) an increased number of daily steps, 3) improved cognitive function, 4) increased VO2max, 5) improved quality of life, and 6) time to initiate dopaminergic medication and the quantity of medication. Third, to test the effects of high intensity endurance exercise on PD over 12 months on biomarkers of dopaminergic neuronal integrity and blood-derived biomarkers of inflammation, and neurotrophic factors. The study design will facilitate the translation of the study results into a meaningful clinical application of clear therapeutic value. 天下科研，唯快不破。 看了上述检索结果，对您有什么启发？赶快行动吧。 如果您需要HS提供类似的选题大数据分析，可阅读下面的推文： 应用这个“外挂”，张医生的选题思路源源不断、文章不断发表！ 关键词： #美国基金解析；#Hanson临床科研；#Healsan医路成长 作者：Amber Wang，助理：ChatGPT 美国Healsan(恒祥医学)，专长于Healsan™医学大数据分析、基于大数据的HansonCR™临床科研支持，以及MedEditing™的医学编辑服务。主要为医院科研处、生物制药公司和医生科学家提供数据分析和SCI报告，成为诸多机构的“临床科研外挂”。 网址：https://healsan.com/ 点击👆；From Bench to Bedside, Healsan Paves the Path. ▼ 支持基金申请和SCI论文发表，推动临床科研的创新与发展。 基于Healsan™文献计量大数据的系列推文，全年安排如下；目前是研究热门靶点系列。 ▲ 每年1-2月 ▲ 每年3-4月 ▲ 每年5-6月 ▲ 每年7-8月 ▲ 每年9-10月 ▲ 每年11-12月 （点击👆图片，进入自己感兴趣的专辑） ▼ 临床科研技巧及文献更新 （点击👆图片，进入自己感兴趣的专辑。或点击“资源”，浏览本公众号所有资源） 更多高质量的医学生物科研、职业发展、及赴美访学留学推文，点击左下角“阅读原文”可见；电子邮箱注册后，可以每天免费收到高质量科研推送。