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
基本信息
- 批准号:2148598
- 负责人:
- 金额:$ 5万
- 依托单位:
- 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:
- 关键词:
项目摘要
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项目更广泛的影响/商业潜力是开发靶向特异性药物,以降低帕金森病中左旋多巴诱导的运动障碍的严重程度和发生率。运动障碍是左旋多巴治疗的一种使人衰弱的副作用,其特征是异常的不自主运动,可干扰全球近1000万帕金森病患者中高达90%的日常活动。考虑到由运动障碍的发展引起的护理人员和患者所感受到的增加的经济负担,以及相关的生活质量降低,为患者提供运动障碍缓解代表了临床中很大程度上未满足的需求。减少运动障碍可能会让一些患者重新获得对生活的更多控制。有些人可能开始自己进食和洗澡,有些人可能再次与他们的孩子或孙子玩耍,还有一些人可能重新获得足够的运动控制权,重返工作岗位。在商业上,运动障碍救济提供了一个机会,重新利用FDA批准的药物到专利的组合和/或配方,增加成功转化为clinic.This的可能性I-Corps项目是基于新的重新利用的双重作用选择性5-羟色胺(5-HT)再摄取抑制剂(SSRI)/5-HT 1A受体激动剂化合物,减少表达和运动障碍的发病率的发展。十多年来的研究已经验证了具有SSRI或5 HT 1A受体激动剂作用的药物能够减少运动障碍,然而,一项突破性发现了证据表明,作用于这两个靶点的药物可以前所未有地减少运动障碍,抑制率超过90%。对患者来说幸运的是,已经确定了两种FDA批准的药物符合这些标准,并在临床前模型中产生了实质性的效果。使用重新设计的药物,而不是新的药物,增加了成功转化为临床的机会,因为这些化合物已经被降低了风险,并进行了安全性和耐受性试验。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,从而减少了数亿美元的开发成本。使用再利用药物更安全、更便宜、更成功,这就是为什么FDA批准的所有新治疗中有30%涉及使用再利用药物的原因。该奖项反映了NSF的法定使命,并通过使用基金会的知识价值和更广泛的影响审查标准进行评估,被认为值得支持。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Christopher Bishop其他文献
The novel analog 1,24(S)-dihydroxyvitamin D2 is as equipotent as 1,25-dihydroxyvitamin D3 in growth regulation of cancer cell lines.
新型类似物 1,24(S)-二羟基维生素 D2 在癌细胞系生长调节方面与 1,25-二羟基维生素 D3 等效。
- DOI:
- 发表时间:
1998 - 期刊:
- 影响因子:2
- 作者:
Y. Levy;Knutson Jc;Christopher Bishop;S. Shany - 通讯作者:
S. Shany
Exploring Gender Roles and Gender Equality within the Evangelical Church
探索福音派教会内的性别角色和性别平等
- DOI:
10.36837/chapman.000037 - 发表时间:
2019 - 期刊:
- 影响因子:2.1
- 作者:
Christopher Bishop - 通讯作者:
Christopher Bishop
DeepSpeed4Science Initiative: Enabling Large-Scale Scientific Discovery through Sophisticated AI System Technologies
DeepSpeed4Science 计划:通过复杂的人工智能系统技术实现大规模科学发现
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
S. Song;Bonnie Kruft;Minjia Zhang;Conglong Li;Shiyang Chen;Chengming Zhang;Masahiro Tanaka;Xiaoxia Wu;Jeff Rasley;A. A. Awan;Connor Holmes;Martin Cai;Adam Ghanem;Zhongzhu Zhou;Yuxiong He;Christopher Bishop;Max Welling;Tie;Christian Bodnar;Johannes Brandsetter;W. Bruinsma;Chan Cao;Yuan Chen;Peggy Dai;P. Garvan;Liang He;E. Heider;Pipi Hu;Peiran Jin;Fusong Ju;Yatao Li;Chang Liu;Renqian Luo;Qilong Meng;Frank Noé;Tao Qin;Janwei Zhu;Bin Shao;Yu Shi;Wen;Gregor Simm;Megan Stanley;Lixin Sun;Yue Wang;Tong Wang;Zun Wang;Lijun Wu;Yingce Xia;Leo Xia;Shufang Xie;Shuxin Zheng;Jianwei Zhu;Pete Luferenko;Divya Kumar;Jonathan Weyn;Ruixiong Zhang;Sylwester Klocek;V. Vragov;Mohammed Alquraishi;Gustaf Ahdritz;C. Floristean;Cristina Negri;R. Kotamarthi;V. Vishwanath;Arvind Ramanathan;Sam Foreman;Kyle Hippe;T. Arcomano;R. Maulik;Max Zvyagin;Alexander Brace;Bin Zhang;Cindy Orozco Bohorquez;Austin R. Clyde;B. Kale;Danilo Perez;Heng Ma;Carla M. Mann;Michael Irvin;J. G. Pauloski;Logan Ward;Valerie Hayot;M. Emani;Zhen Xie;Diangen Lin;Maulik Shukla;Thomas Gibbs;Ian Foster;James J. Davis;M. Papka;Thomas Brettin;Prasanna Balaprakash;Gina Tourassi;John P. Gounley;Heidi Hanson;T. Potok;Massimiliano Lupo Pasini;Kate Evans;Dan Lu;D. Lunga;Junqi Yin;Sajal Dash;Feiyi Wang;M. Shankar;Isaac Lyngaas;Xiao Wang;Guojing Cong;Peifeng Zhang;Ming Fan;Siyan Liu;A. Hoisie;Shinjae Yoo;Yihui Ren;William Tang;K. Felker;Alexey Svyatkovskiy;Hang Liu;Ashwin Aji;Angela Dalton;Michael Schulte;Karl Schulz;Yuntian Deng;Weili Nie;Josh Romero;Christian Dallago;Arash Vahdat;Chaowei Xiao;Anima Anandkumar;R. Stevens - 通讯作者:
R. Stevens
Effects of genetic knockdown of the serotonin transporter on established L-DOPA-induced dyskinesia and gene expression in hemiparkinsonian rats
5-羟色胺转运体基因敲除对已建立的左旋多巴诱导的帕金森病大鼠运动障碍及基因表达的影响
- DOI:
10.1016/j.neuropharm.2024.110227 - 发表时间:
2025-03-15 - 期刊:
- 影响因子:4.600
- 作者:
Grace McManus;Ashley Galfano;Carla Budrow;Natalie Lipari;Kuei Y. Tseng;Fredric P. Manfredsson;Christopher Bishop - 通讯作者:
Christopher Bishop
The burden of the present in Gareth Brookes, The Dancing Plague
加雷斯·布鲁克斯《跳舞的瘟疫》中当下的负担
- DOI:
10.1080/1472586x.2022.2050101 - 发表时间:
2022 - 期刊:
- 影响因子:0.7
- 作者:
Christopher Bishop - 通讯作者:
Christopher Bishop
Christopher Bishop的其他文献
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{{ truncateString('Christopher Bishop', 18)}}的其他基金
Quasiconformal analysis, optimal triangulations and fractal geometry
拟共形分析、最优三角剖分和分形几何
- 批准号:
2303987 - 财政年份:2023
- 资助金额:
$ 5万 - 项目类别:
Standard Grant
Quasiconformal Constructions in Analysis and Dynamics
分析和动力学中的拟共形结构
- 批准号:
1906259 - 财政年份:2019
- 资助金额:
$ 5万 - 项目类别:
Continuing Grant
Geometric Problems in Conformal Analysis, Dynamics, and Probability
共形分析、动力学和概率中的几何问题
- 批准号:
1608577 - 财政年份:2016
- 资助金额:
$ 5万 - 项目类别:
Continuing Grant
Quasiconformal methods in analysis, geometry and dynamics
分析、几何和动力学中的拟共形方法
- 批准号:
1305233 - 财政年份:2013
- 资助金额:
$ 5万 - 项目类别:
Continuing Grant
Analysis of conformal and quasiconformal maps
共形和拟共形映射的分析
- 批准号:
1006309 - 财政年份:2010
- 资助金额:
$ 5万 - 项目类别:
Standard Grant
Geometry of Conformal and Quasiconformal Mappings
共形和拟共形映射的几何
- 批准号:
0405578 - 财政年份:2004
- 资助金额:
$ 5万 - 项目类别:
Standard Grant
Geometry of Conformal and Quasiconformal Mappings
共形和拟共形映射的几何
- 批准号:
0103626 - 财政年份:2001
- 资助金额:
$ 5万 - 项目类别:
Continuing Grant
Mathematical Sciences: Postdoctoral Research Fellowship
数学科学:博士后研究奖学金
- 批准号:
8705957 - 财政年份:1987
- 资助金额:
$ 5万 - 项目类别:
Fellowship Award
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