罕见病研究与孤儿药研发  

Rare disease research and orphan drug discovery

作　　者：冯时[1] 刘爽[1] 弓孟春[1] 张抒扬[1] 

机构地区：[1]中国医学科学院北京协和医学院,北京协和医院中心实验室,北京100730

出　　处：《国际药学研究杂志》2017年第2期95-100,共6页Journal of International Pharmaceutical Research

基　　金：国家重点研发计划精准医学研究重点专项"罕见病临床队列研究"资助项目(2016YFC0901500);上海市出生缺陷防治重点实验室开放课题(16DZKF1007)

摘　　要：孤儿药缺乏一直是罕见病治疗中的瓶颈问题,孤儿药市场具有极高的商业潜力。目前全球范围内多个国际组织合作简化孤儿药专利申请过程,推动孤儿药研发、上市加速发展。中国国家罕见病注册系统(NRDRS)队列研究项目采用队列研究方法,可最大程度地为孤儿药临床试验提供便利。罕见病发病机制的研究将为孤儿药的研发提供新的策略和切入点,尤其是孤儿药中的基因治疗和酶替代疗法,其作用靶点极大依赖于对罕见病致病机制的了解。除此之外,罕见病机制的研究也将推动常见疾病药物适应证拓展,使部分常见疾病药物重定位为孤儿药。相应地,罕见病致病机制也可能为常见疾病的新药开发提供新的作用靶点。对于经过临床试验验证治疗效果、但作用机制尚不清晰的新药,罕见病致病机制也可提供新的思路,从而有助于解释其作用机制。此外,由于孤儿药批准、上市速度远优于常见疾病药物,许多药物最初作为孤儿药上市,但后期适应证拓展使其同样可用于治疗常见疾病,有力推动了制药产业的发展。在精准医学思想的指导下,随着中国NRDRS的建立及完善,罕见病基因型与表型之间的关系将日趋分明,这将有效助力孤儿药的研发,进而推动中国医药产业的整体迈进。Rare diseases are the major challenges we face today and the difficulties in the treatments mainly lie in the shortage of orphan drugs. The growing awareness of the need for pharmaceutical products means the orphan drug market has great commercial potential. Currently,multiple international organizations cooperate to reduce the redundancies and the administrative load in submitting applications for orphan drug designation,aiming to accelerate the global legislation of the orphan drugs. In China,a nation-wide registry system,the National Rare Diseases Registry System of China（NRDRS）,and the cohort study based on the registry system will greatly facilitate both the rare disease research and the following clinical trials of orphan drugs. The study of the rare disease pathogenic mechanisms will benefit the development of orphan drugs,especially in gene therapy and enzyme replacement treatment,the targets of which largely depend on the understanding of the disease pathogenesis. It will not only advocate the repurposing of the common drugs,so as to be approved as orphan drugs,but also expand the scope of the common drug targets,solving the inherent problems.Furthermore,though the efficacy and safety of orphan drugs may be verified by clinical trials,the underlying mechanism can only be explained with the help of the study of the rare diseases. Besides,thanks to the superiority of the marketing and legislation of the or-phan drugs,many medicines may be approved as orphan drugs at the very beginning,but with the expansion of the indications,they may turn out to be effective in various common diseases. Therefore,orphan drugs are also beneficial to the development of the overall pharmaceutical industry. In the era of the precision medicine,the set up of the NRDRS of China will help clarify the correlation between the phenotype and the genotype,strongly assist the industrial delivery of orphan drugs,and may eventually lead to the enhancement of the pharmaceutical industry in China.

关 键 词：罕见病 孤儿药 队列研究 精准医学 中国国家罕见病注册系统 

分 类 号：R95[医药卫生—药学] R97