I-Corps: Repurposing Serotoninergic Compounds for Improved Treatment of Parkinson's Disease

I-Corps：重新利用血清素能化合物以改善帕金森病的治疗

• 批准号: 2148598
• 负责人: Christopher Bishop
• 金额: $ 5万
• 依托单位: SUNY at Binghamton
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2148598&HistoricalAwards=false
• 关键词: Corps; Repurposing; Serotoninergic; Compounds; Improved

The broader impact/commercial potential of this I-Corps project is the development of target-specific drugs that reduce severity and incidence of levodopa-induced dyskinesia in Parkinson’s disease. Dyskinesia is a debilitating side effect of levodopa therapy characterized by abnormal involuntary movements that can interfere with daily activities present in up to 90% of nearly 10 million Parkinson’s disease patients worldwide. Considering the increased economic burden felt by caregivers and patients resulting from the development of dyskinesia, in addition to the associated reductions in quality of life, providing dyskinesia relief to patients represents a largely unmet need in the clinic. Reducing dyskinesia may allow some patients to regain more control of their lives. Some may be able to begin feeding and bathing themselves again, others may once again play with their children or grandchildren, and others may regain enough movement control to return to work. Commercially, dyskinesia relief presents an opportunity to repurpose FDA-approved drugs into patentable combinations and/or formulations that increase the likelihood of successful translation into the clinic.This I-Corps project is based on the development of newly repurposed dual-action selective serotonin (5-HT) reuptake inhibitor (SSRI)/5-HT1A receptor agonist compounds that reduce the expression and incidence of dyskinesia. Over a decade of research has validated the capability of drugs with either SSRI or 5HT1A receptor agonist actions to reduce dyskinesia, however, a breakthrough discovery has uncovered evidence that drugs acting on both targets produce an unprecedented reduction of dyskinesia exceeding 90% suppression. Fortunately for patients, two FDA-approved drugs have been identified that meet these criteria and produce substantial effects in pre-clinical models. Using repurposed, as opposed to novel, drugs increase chances of successful translation into the clinic, as these compounds already have been de-risked and trialed for safety and tolerability. In addition, the mechanisms of action of these drugs are well validated through prior trials, reducing development costs by hundreds of millions of dollars. The use of repurposed drugs is safer, cheaper, and more successful, which is why 30% of all newly-FDA approved treatments involve the use of repurposed drugs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该I-Corps项目的更广泛的影响/商业潜力是开发针对特定目标的药物，这些药物降低了帕金森氏病中左旋多巴引起的运动障碍的严重程度和发病率。运动障碍是左旋多巴疗法的一种使人衰弱的副作用，其特征是异常的非自愿运动，可以干扰全球近1000万帕金森氏病患者的日常活动。考虑到，除了相关的生活质量降低外，护理人员和患者的经济伯恩感染者和患者的经济增强了，为患者提供了发育不良的疾病，这在诊所中的需求在很大程度上是未满足的需求。减少运动障碍可能会使某些患者能够继续更多地控制自己的生活。有些人可能能够再次开始喂食和洗澡，另一些人可能会再次与孩子或孙子一起玩，而另一些人可能会重复运动的足够的动作控制以重返工作岗位。 Commercially, dyskinesia relief presents an opportunity to reform FDA-approved drugs into patentable combinations and/or formulas that increase the likelihood of successful translation into the clinic.This I-Corps project is based on the development of newly repurposed dual-action selective serotonin (5-HT) reuptake inhibitor (SSRI)/5-HT1A receptor agonist compounds that reduce the运动障碍的表达和发生率。十多年来的研究已经验证了SSRI或5HT1A受体激动剂作用的药物能力减少运动障碍，但是，突破性的发现发现了作用于这两个靶标的药物会导致不前前期的运动障碍的药物超过90％的抑制作用。幸运的是，对于患者，已经确定了符合这些标准并在临床前模型中产生实质性影响的两种FDA批准的药物。与新颖的药物相比，使用重新塑造的药物增加了成功转化为诊所的机会，因为这些化合物已经被脱离风险和试验，并试用了安全性和耐受性。此外，这些药物的作用机制通过先前的试验得到了很好的验证，将开发成本降低了数亿美元。使用重新定位的药物的使用更安全，更便宜且更成功，这就是为什么所有新近FDA批准的治疗方法中有30％涉及使用重新使用的药物的原因。这项奖项反映了NSF的法定任务，并通过使用基金会的知识分子和更广泛的影响审查标准来通过评估来诚实地诚实地支持。