Division of Pediatric Pulmonology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, United States.
Pharmacol Res. 2011 Sep;64(3):176-9. doi: 10.1016/j.phrs.2011.03.019. Epub 2011 Apr 20.
The United Nation's Millennium Development Goal of tuberculosis (TB) elimination by 2050 may be a realizable goal by concerting efforts of the numerous stakeholders involved in the development of novel antituberculous therapeutics. Improving pre-clinical models by the research community is one aspect of the drug development pipeline that will continue to require refinement. Better in vitro and animal models are needed to expand the chemical scaffolds of anti-TB agents. These constructs must be designed and utilized in a manner that is also pertinent to the pediatric population by addressing varying age-based drug metabolism rates. Novel technologies that utilize nanomedicine and genomic research may as well have a significant impact on future therapeutics; however, their development must acknowledge the key populations whose underlying disease pathology continues to drive the pandemic - both adults and children with latent TB, HIV/AIDS and diabetes. Challenging the long-standing orthodoxy of applying equivalent TB treatments for standard first line regimens among the adult and pediatric populations must also continue to be a major focus in future drug development strategies. Studies that include pediatric populations will require a greater variety of medication formulations, biomarkers that do not rely on sputum production and diagnostic technologies that are efficacious in paucibacillary disease. Significant programmatic barriers currently exist in key aspects of the described drug development pipeline, but strategic approaches can overcome these roadblocks - including the complex regulatory requirements involving the inclusion of children in drug trials. All such endeavors will require not only more focused research initiatives, but greater institutional support from the pharmaceutical industry, non-governmental organizations and national health sectors.
联合国 2050 年消除结核病(TB)的千年发展目标,通过协调参与新型抗结核治疗药物开发的众多利益相关者的努力,可能成为一个可实现的目标。研究界通过改进临床前模型,是药物开发管道的一个方面,将继续需要改进。需要更好的体外和动物模型来扩展抗结核药物的化学支架。这些结构必须以与儿科人群相关的方式进行设计和利用,以解决不同年龄的药物代谢率差异。利用纳米医学和基因组研究的新技术也可能对未来的治疗产生重大影响;然而,它们的开发必须认识到关键人群,其潜在的疾病病理继续推动大流行-潜伏性结核病、艾滋病毒/艾滋病和糖尿病的成人和儿童。在未来的药物开发策略中,还必须继续挑战长期以来的传统观念,即对成人和儿科人群应用等效的结核病治疗方案。包括儿科人群的研究将需要更多种类的药物制剂、不依赖于痰产生的生物标志物和在少菌病中有效的诊断技术。在描述的药物开发管道的关键方面,目前存在重大的计划障碍,但战略方法可以克服这些障碍-包括涉及将儿童纳入药物试验的复杂监管要求。所有这些努力不仅需要更集中的研究计划,还需要制药行业、非政府组织和国家卫生部门提供更多的机构支持。