PBI Manufacture Core

该计划项目设想在人类受试者身上进行两个小型的概念验证I期临床试验。 为了促进这项计划项目赠款的工作，病理公司将负责 生产研究用新药所需的制造、质量控制和质量保证。这 成分包括，复方(S)的制造，药物(S)的包装，稳定性试验， 制作临床研究人员手册，并对两项试验的IND进行归档。第一次试验是设想的 多胺生物合成抑制剂PA-001参与HIV相关性痴呆及相关疾病的发生 综合症。PA-001在恒河猴模型中显示出良好的抗SIV脑炎活性(见 项目2：更多细节的动物模型研究)。第二次试验的化合物将根据 根据该计划项目头两年进行的体外和动物研究的结果， 但也将是多胺生物合成的抑制剂。病理有限责任公司很幸运有权对 并将包括多胺类似物CG47在内的许多PBI商业化，PBI制造核心将 确保这些多胺类似物有足够的数量和质量可供比较 与PA-001的研究更全面地描述在本计划项目赠款的项目1和2中。以提供 药物病理公司将由弗雷德里克·约翰逊博士协助，他在 小分子和生物制药产品的制造和质量保证测试。

This program project envisions running two small proof of concept phase I clinical trials in human subjects. To facilitate the work of this program project grant, Pathologica will be responsible for all aspects of the manufacture, quality control, and quality assurance required to produce an investigational new drug. This component includes, the manufacture of the compound(s), packaging of the drug(s), stability testing, production of clinical investigator brochures, and filing of the INDs for both trials. The first trial is envisioned to involve the polyamine biosynthesis inhibitor PA-001 in the setting of HIV associated dementia and related syndromes. PA-001 has shown excellent activity against SIV encephalitis in rhesus macaque model (see Project 2: Animal model studies for more details). The compound for the second trial will be chosen based on the results of the in vitro and animal studies performed during the first two years of the program project, but will also be a polyamine biosynthesis inhibitor. Pathologica LLC is fortunate to have rights to evaluate and commercialize many PBIs including the polyamine analog CG47, and the PBI manufacture core will ensure that sufficient quantity and quality of these polyamine analogs will be available for comparative studies with PA-001 as described more fully in Projects 1 and 2 of this program project grant. To provide the drugs Pathologica will be assisted by Dr Fredrick Johnson, who has more than 20 years of experience in the manufacture and quality assurance testing of both small molecule and biological pharmaceutical products.