Therapeutics for Rare and Neglected Diseases - Science

六个TRND试点项目的工作仍在继续，选择这些项目是为了在征集之前建立具有项目阶段、疾病类型和合作者多样性的程序。这六项试验计划包括： 1.尼曼-皮克病--一种罕见疾病 2.遗传性包涵体肌病，一种罕见疾病 3.贾第鞭毛虫病--一种被忽视的疾病 4.血吸虫病--一种被忽视的疾病 5.镰状细胞病，一种罕见的疾病 6.慢性淋巴细胞白血病，一种罕见的疾病 2011财年，首两个TRND项目征集成功启动。这些征集活动共收到125份建议书；这些建议书来自工业界、学术界、政府实验室和非营利机构。这些提案由一个外部专家小组审查。选择了10个项目进行协作，代表了不同的项目类型： 1.杜氏肌营养不良症，一种罕见疾病2个不同的项目 2.脆性X综合征--一种罕见疾病 3.隐球菌性脑膜炎--一种被忽视的疾病 4.CBF白血病，一种罕见疾病 新生儿单纯疱疹病毒，一种罕见的疾病 6.罕见的肺泡蛋白沉积症 7.进行性骨化性纤维发育不良，一种罕见的疾病 8.血吸虫病--一种被忽视的疾病 9.肌酸转运蛋白缺乏症，一种罕见的疾病 2012财年期间还启动了第三次征集活动，将在2013财年期间选定合作建议书。 在启动的两年内，两个项目(用于镰刀细胞疾病的AES-103和用于慢性淋巴细胞白血病的Auranofin)成功地向FDA申请了IND，这两个项目的首次人体临床试验正在进行中。另外两个项目正在按计划在2013财年提交IND。一个项目因未能达到里程碑目标而被叫停。所有其他项目都已达成合作协议和里程碑协议，并正在实现中期里程碑并按时间表取得进展。 针对这些罕见或被忽视的适应症的治疗方法的开发已经并将继续涉及由TRND执行和/或提供的下列领域的资源： 1.药物化学优化 2.药代动力学/药效学 3.毒理学 4.给药 5.提法 6.监管支持 7.项目管理 除了实现其特定于项目的目标外，TRND还开发了提高翻译过程效率的新技术和协作范例。例如，两个项目正在开发新的平台技术，可用于开发治疗各种其他人类疾病的疗法。 以下领域的业务工作也在继续： 1.确定跨国立卫生研究院工作人员咨询小组(TAG)的治理并举行会议。 2.参加与有兴趣了解TRND的公司、学术科学家和疾病界个人举行的多次会议。 3.探索与区域发展方案中感兴趣的利益攸关方建立潜在的伙伴关系，以寻找利用区域发展方案活动的机会。 4.起草和最后确定一份TRND研究与开发申请，以获得未来研究的资金。 5.设计和评估将新项目纳入TRND管道的招标和相关支助系统。

Work has continued on the six TRND pilot projects, which were chosen to establish processes in advance of solicitation with diversity of project stage, type of disease, and collaborators. The six pilot projects include: 1. Niemann-Pick C Disease, a rare disease 2. Hereditary Inclusion Body Myopathy, a rare disease 3. Giardiasis, a neglected disease 4. Schistosomiasis, a neglected disease 5. Sickle Cell Disease, a rare disease 6. Chronic Lymphocytic Leukemia, a rare disease In FY11, the first two TRND project solicitations were successfully launched. One hundred twenty-five proposals were received in response to these solicitations; these proposals came from industry, academia, government laboratories, and not-for-profit institutions. The proposals were reviewed by an external panel of experts. Ten projects were selected for collaboration, representing a diverse group of project types: 1. Duchenne Muscular Dystrophy, a rare disease 2 different projects 2. Fragile X Syndrome, a rare disease 3. Cryptococcal meningitis, a neglected disease 4. CBF leukemia, a rare disease 5. Neonatal Herpes Simplex Virus, a rare disease 6. Pulmonary Alveolar Proteinosis, a rare disease 7. Fibrodysplasia Ossificans Progressiva, a rare disease 8. Schistosomiasis, a neglected disease 9. Creatine Transporter Defect, a rare disease A third solicitation was also launched during FY12, and proposals will be selected for collaboration during FY13. Within two years of initiation, two projects (Aes-103 for Sickle Cell Disease and Auranofin for Chronic Lymphocytic Leukemia) yielded successful IND applications to the FDA, and first in-human clinical trials are ongoing in both. Two additional projects are on schedule for IND submission in FY13. One project has been discontinued for failure to meet milestones. All other projects have had collaborative and milestone agreements put in place, and are achieving interim milestones and progressing according to schedules. The development of therapeutics for these rare or neglected indications has involved and will continue to involve resources in the following areas, performed and/or provided by TRND: 1. Medicinal Chemistry Optimization 2. Pharmacokinetics / Pharmacodynamics 3. Toxicology 4. Dosing 5. Formulation 6. Regulatory Support 7. Project Management In addition to meeting its project-specific goals, TRND has developed novel technologies and collaborative paradigms that improve the efficiency of the translational process. For example, two projects are developing novel platform technologies that can be used to develop therapeutics to treat a variety of other human disorders. Operational work also continued in the following areas: 1. Determining governance of TRND and holding meetings of the Trans-NIH Staff Advisory Group (TAG). 2. Participating in numerous meetings with companies, academic scientists, and individuals from disease communities interested in learning about TRND. 3. Exploring potential partnerships with interested stakeholders in RNDs to seek opportunities to leverage TRND activities. 4. Crafting and finalizing a TRND Research & Development Request for Proposals through which future research will be funded. 5. Designing and evaluating the solicitation and associated support system to bring new projects into the TRND pipeline.