Hesperos Diversity Supplement forgrant number 1 R44AG071386
Hesperos 多样性补充补助金编号 1 R44AG071386
基本信息
- 批准号:10577655
- 负责人:
- 金额:$ 16.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-15 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdverse drug eventAdverse eventAlgorithmsAlzheimer&aposs DiseaseAnti-CholinergicsBiological AssayBlood - brain barrier anatomyCaringCause of DeathCellsClinicalCognitiveCollaborationsCytochrome P450DementiaDoseDrug InteractionsDrug KineticsDrug usageElderlyFrail ElderlyHealthcareHospitalizationHumanIndividualIntakeJournalsKnowledgeLearningLegal patentLiteratureLiverLong-Term PotentiationMeasurementMedicalMedical Care CostsMemoryMetabolicModelingNeuronsPatientsPeer ReviewPharmaceutical PreparationsPharmacodynamicsPharmacologyPolypharmacyProductionPropertyPublicationsRegimenRiskSystemTestingTherapeuticadverse event riskbaseburden of illnesscomorbiditydementia riskdrug metabolismhealth care modelhigh riskimprovedin vitro Modelinformation processinginnovationmutantolder patientpre-clinicalrisk stratificationscreeningtooltreatment duration
项目摘要
Project Summary/Abstract
The burden associated with polypharmacy and inappropriate drug use is the third leading cause of death in
the USA. With advanced age, providing medical care can present challenges as these patients are at risk for
comorbidities and have the largest burden of illness. There is the unmet need of having proper approaches and
innovative tools to identify not only drugs but also drug regimens associated with the highest risk of drug-related
adverse events (ADEs). Medications with anticholinergic properties have frequently been cited in the literature
as a major cause for an increase in ADEs. The resulting prescription cascade increases the risk of multi-drug
interactions on enzymatic systems (such as the Cytochrome P450 superfamily) used to metabolize many drugs
with anticholinergic properties. Hence, innovative approaches and tools developed to address these situations
should consider not only individual drug pharmacological properties but account for conditions associated with
the impact of multi-drug intake and interactions. We seek to use Hesperos’ patented multi-organ functional
systems to investigate drug-induced dementia and Alzheimer’s disease (AD) in terms of deficits in basic
information processing in the presence of anticholinergic drugs in collaboration with Tabula Rasa HealthCare
(TRHC) and our AD consultant, Dr. Dave Morgan at MSU. TRHC has created basic and clinical algorithms that
help quantitatively score the risk of ADEs, including an assessment of drug anticholinergic properties and multi-
drug interactions, with a special look at competitive inhibition. Increased knowledge on these factors through the
conduct of proposed studies with Hesperos’s experimental systems shall improve the predictivity of risk
stratification possibilities, help decrease the risk of ADEs in elderly patients, decrease hospitalizations, and
reduce overall medical costs. The value of TRHC’s CDSS and risk stratification strategy has been demonstrated
by publications in peer-review journals and filing of three patents. There are few in vitro models that examine
anticholinergic drug properties in the CNS while assessing their association between anticholinergic burden and
risk of dementia, including AD. Thus, a preclinical screening model based on functional assays composed of
normal and AD mutant human cells to evaluate the effects of anticholinergic drugs in conditions mimicking
aspects of AD enables a platform for understanding multiplicative effects and to inform TRHC’s
pharmacokinetic/pharmacodynamic clinical models. No other models assessing the anti-cholinergic burden of
drugs take into account their dose, duration of treatment and concomitant drug administration leading to a change
in their disposition. Changes in Long-term Potentiation will be used as the cognitive readout as it is a functional
measurement known to correlate with changes in memory and learning. The integration of this neuronal module
with a system that includes a blood-brain-barrier and a liver with functional enzymatic systems would allow testing
of combinational therapeutics and variability in their metabolic disposition due to expected multi-drug interactions
impacting drug metabolism systems as observed in patients with polypharmacy.
项目总结/文摘
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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James J Hickman其他文献
James J Hickman的其他文献
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{{ truncateString('James J Hickman', 18)}}的其他基金
Investigating the role of Alzheimer's disease familial mutations in neuromuscular physiology
研究阿尔茨海默病家族突变在神经肌肉生理学中的作用
- 批准号:
10620712 - 财政年份:2022
- 资助金额:
$ 16.27万 - 项目类别:
Investigating the role of Alzheimer's disease familial mutations in neuromuscular physiology
研究阿尔茨海默病家族突变在神经肌肉生理学中的作用
- 批准号:
10448570 - 财政年份:2022
- 资助金额:
$ 16.27万 - 项目类别:
Modulatory Role of Blood-Brain-Barrier and Enzymatic Activity in an Innovative Human Model of Cholinergic Drug Induced Dementia
血脑屏障和酶活性在胆碱能药物诱发痴呆的创新人类模型中的调节作用
- 批准号:
10258975 - 财政年份:2021
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Populating MPS database with data from multi-organ, human-on-a-chip microphysiological systems
用来自多器官、人体芯片微生理系统的数据填充 MPS 数据库
- 批准号:
10435269 - 财政年份:2021
- 资助金额:
$ 16.27万 - 项目类别:
Modulatory Role of Blood-Brain-Barrier and Enzymatic Activity in an Innovative Human Model of Cholinergic Drug Induced Dementia
血脑屏障和酶活性在胆碱能药物诱发痴呆的创新人类模型中的调节作用
- 批准号:
10467040 - 财政年份:2021
- 资助金额:
$ 16.27万 - 项目类别:
Multi-organ human-on-a-chip system to address overdose and acute and chronic efficacy and off-target toxicity
多器官人体芯片系统解决用药过量、急慢性疗效和脱靶毒性问题
- 批准号:
10351973 - 财政年份:2019
- 资助金额:
$ 16.27万 - 项目类别:
Drug-drug interactions for antivirals with opioids and Narcan in a 5- organ human-on-a-chip model
抗病毒药物与阿片类药物和纳洛酮在 5 器官芯片模型中的药物相互作用
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10224388 - 财政年份:2019
- 资助金额:
$ 16.27万 - 项目类别:
Human on a chip systems to investigate disease comorbidities common in the aged population
人类芯片系统研究老年人群中常见的疾病合并症
- 批准号:
10402384 - 财政年份:2018
- 资助金额:
$ 16.27万 - 项目类别:
Human on a chip system to investigate genetic risk factors in Alzheimer's disease
人类芯片系统研究阿尔茨海默病的遗传风险因素
- 批准号:
9628532 - 财政年份:2018
- 资助金额:
$ 16.27万 - 项目类别:
Development of an integrated 4-organ animal model
综合四器官动物模型的开发
- 批准号:
9986123 - 财政年份:2018
- 资助金额:
$ 16.27万 - 项目类别:
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