Primate Model for Pharmaceutical Development

描述(由申请人提供)：分子医学和基因组研究的进展有望为人类疾病的治疗产生令人兴奋的新策略。关于临床前研究数据的一个重要问题是，结果可能不能预测未来的临床结果。动物和人类在解剖、生理和病理过程上存在许多差异。 我们的STTR计划的目标是在猴子身上建立一种新的临床前研究模型。这种长期有器械、有意识的猴子模型将密切模拟在人类患者中观察到的充血性心力衰竭的过程，充血性心力衰竭是美国死亡和发病率的主要原因。显然，这个模型不仅有助于阐明心脏病的机制，而且还将为评估潜在的人类新干预措施提供一个系统。还可以进行药效学和药动学研究，以及安全性和毒理学评估。 第一阶段STTR项目证明了这样一个假设，即心肌梗死(MI)与快速心室起搏相结合可以在有器械的清醒猴子中诱导慢性心肌缺血，导致终末期心力衰竭。第二阶段的研究将进一步描述这一模型，特别是关于心肌重塑的现象，并可能导致识别与心脏细胞生存和死亡有关的基因。 为了实现第二阶段的目标，这项研究将使用最先进的、生理、基因组和病理学的猴子实验方法。这一第二阶段项目将使新的商业企业Vasade Biosciences能够为生物技术和制药公司的早期临床前需求提供有价值的商业合同研究服务。

DESCRIPTION (provided by applicant): Advances in molecular medicine and genomic research promise to produce exciting new strategies for the treatment of human diseases. One significant concern regarding preclinical research data is that the results may not be predictive of future clinical outcomes. Many differences in anatomy, physiology and pathological processes exist between animals and humans. The goal of our STTR proposal is to set up a novel preclinical research model in monkeys. This chronically instrumented, conscious monkey model will closely mimic the process of congestive heart failure observed in human patients, which is a leading cause of mortality and morbidity in the US. Clearly, this model will help not only to elucidate the mechanisms of the heart disease, but also will provide a system for the assessment of potential new interventions in man. Pharmacodynamic and pharmacokinetic studies, as well as safety and toxicology assessments also may be performed. The Phase I STTR project proved the hypothesis that combined myocardial infarction (MI) with rapid ventricular pacing can induce chronic myocardial ischemia leading to end stage heart failure in instrumented, conscious monkeys. The Phase II study will further characterize this model, particularly regarding the phenomenon of myocardial remolding, and may lead to the identification of genes involved in cardiac cell survival and death. To achieve the phase II goals, the study will use state-of-art, physiological, genomic and pathological experimental approaches in monkeys. This Phase II project will enable the new business venture, Vasade Biosciences, to provide a valuable commercial contract research service for the early preclinical needs of biotechnology and pharmaceutical companies.