Developmental Clinical Studies: Inhibition of C-reactive protein for treatment of cardiovascular & inflammatory diseases

c反应蛋白（CRP）是血液中正常的微量成分，在大多数类型的损伤、感染或炎症后，其浓度会急剧增加。我们已经发现，人类的c反应蛋白可以使这种损伤恶化，并在心脏病发作和中风的动物模型中证明了这一点。有令人信服的临床证据表明，CRP在人类疾病中具有相同的破坏性作用，抑制它将对多种疾病的治疗做出重大贡献。因此，我们设计了一个新的小分子药物家族，称为bis（磷胆碱）-烷烃，它抑制CRP的不良反应，并在动物模型中有效。我们现在建议开发最佳药物，双（磷胆碱）辛烷，用于临床试验。寻求资金的所需开发步骤是药物的制药、临床前测试、毒理学和符合监管要求的配方，并首先在健康成年志愿者中进行人体研究。该方案将提供一种符合伦理和监管要求的药物，用于在接受所有其他最先进治疗的首次心脏病发作住院患者中进行临床试验。我们对这项试验有详细的计划，但现在不寻求资金。对药物开发的严格监管意味着，现在需要的工作不能在学术机构进行，而只能在制药公司或合同研究组织进行，这些组织专门从事药物生产和测试。因此，我们将把药物的生产、临床前测试和首次人体研究外包给选定的商业公司。成功将严重依赖于使用最好的公司和非常有效的项目管理。我们很幸运的是，共同申请人之一Chris Swain博士在行业药物开发方面拥有长期的成功经验，并担任独立顾问。他将通过Advocates Ltd(该领域领先的咨询公司，为UCL Business PLC （UCL的技术转让部门）提供咨询服务，得到其他专门从事不同开发任务的外部顾问的全程支持。几家大型制药公司和一些制药公司的投资者都非常渴望看到我们的初步临床结果。积极的发现将导致迅速的商业化和获得许可的新药，这将使首席申请人佩皮斯教授40年来对MRC研究的持续支持达到顶峰。

C-reactive protein (CRP), a normal trace constituent of the blood, increases in concentration dramatically following most types of injury, infection or inflammation. We have discovered that human CRP can make such injury worse and have demonstrated it in animal models of heart attack and stroke. There is compelling clinical evidence that CRP has the same damaging effect in human diseases and that its inhibition will make a major contribution to management of a wide range of conditions. We therefore designed a family of new small molecule drugs, called bis(phosphocholine)-alkanes, which inhibit the adverse effects of CRP and are efficacious in animal models. We now propose to develop the optimal drug, bis(phosphocholine) octane, for clinical testing. The required development steps, for which funding is sought, are pharmaceutical manufacture of the drug, pre-clinical testing, toxicology and formulation to comply with regulatory requirements, and first into man studies, in healthy adult volunteers. This programme will provide a medicine which complies with the ethical and regulatory requirements for clinical testing in patients admitted to hospital with a first heart attack who are receiving all other state of the art treatment. We have detailed plans for this trial but do not seek funding for it now. The rigorous regulation of drug development means that the work now needed cannot be conducted in academic institutions but only in pharmaceutical companies or contract research organisations, which specialise in drug manufacture and testing. We shall therefore outsource to selected commercial companies, the production, pre-clinical testing and first into man studies of the drug. Success will critically depend on using the best companies and on very effective project management. We are fortunate that one of the co-applicants, Dr Chris Swain, has a long track record of successful experience in drug development in industry and as an independent consultant. He will be supported throughout by other external consultants specialised in each of the different development tasks, through the services of Advocates Ltd, a leading consultancy firm in this field which advises UCL Business PLC, the technology transfer arm of UCL. Several large pharmaceutical companies and also some investors in pharma company creation are very keen to see our initial clinical results. Positive findings leading to prompt commercialisation and a licensed new medicine will culminate 40 years of continuous MRC support for the research of Professor Pepys, the lead applicant.