Therapeutics for Rare and Neglected Diseases - Science

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与不同的项目阶段、疾病类型和合作者建立程序。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.贾第虫病，一种被忽视的疾病(项目完成) 4.血吸虫病--一种被忽视的疾病(项目中止) 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。共收到125份建议书，以回应这些邀请。这些建议来自工业界、学术界、政府实验室和非营利性机构。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，一种罕见的疾病(两个不同的项目；一个终止) 2.脆性X综合征，一种罕见疾病(项目终止) 3.隐球菌性脑膜炎--一种被忽视的疾病 4.罕见疾病--CBF白血病 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 在2012财年期间启动了第三次征集活动，收到了来自工业界、学术界、政府实验室和非营利性机构的75份申请。经过严格审查，在2013财年选择了四个项目进行协作： 1.罕见的视网膜色素变性(两个不同的项目) 2.罕见的甲状旁腺功能减退症 3.豹子综合症，一种罕见的疾病 在启动的两年内，四个项目(用于镰刀细胞疾病的AES-103；用于慢性淋巴细胞白血病的Auranofin；用于Niemann-Pick C型的环糊精；以及用于遗传性包涵体肌病的DEX-M74)成功地向FDA申请了IND，所有四个项目的首次人体临床试验都在进行中。一个试点项目(贾第虫病)在成功完成项目里程碑后被终止，而另一个试点项目(血吸虫病)因未能达到里程碑而被中止。所有其他项目都有合作协议和里程碑协议，正在实现中期里程碑，并按时间表进展。2011财年通过的两个项目(杜氏肌营养不良症；脆性X综合征)已从TRND组合中停止。Duchenne肌营养不良症合作伙伴现在能够在没有进一步TRND支持的情况下执行未来的步骤，该项目正在按计划进行。由于合作者业务战略的重新调整，脆性X综合征被终止。 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还支持开发新技术和协作范例，以提高翻译过程的效率。例如，两个项目代表了新的平台技术，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.举行跨国立卫生研究院工作人员咨询小组会议，以在评估征求的建议期间获得指导和对生物/疾病领域的具体见解。 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.起草并最终确定一份完善的TRND研究与开发请求，以获得未来研究的资金。 5.评估和改进招标和相关支助制度，以将新项目纳入TRND管道。

Work continued on the TRND pilot projects, which were chosen to establish processes in advance of solicitation with a 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 (project completed) 4. Schistosomiasis, a neglected disease (project discontinued) 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; one discontinued) 2. Fragile X Syndrome, a rare disease (project discontinued) 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 launched during FY12, which received 75 applications from industry, academia, government laboratories, and not-for-profit institutions. After rigorous review, four projects were selected in FY13 for collaboration: 1. Retinitis Pigmentosa, a rare disease (2 different projects) 2. Hypoparathyroidism, a rare disease 3. LEOPARD Syndrome, a rare disease Within two years of initiation, four projects (Aes-103 for Sickle Cell Disease; Auranofin for Chronic Lymphocytic Leukemia; Cyclodextrin for Niemann-Pick Type C; and DEX-M74 for Hereditary Inclusion Body Myopathy) yielded successful IND applications to the FDA, and first in-human clinical trials are ongoing in all four. One pilot project (Giardiasis) has been discontinued after successful completion of project milestones, while another pilot project (Schistosomiasis) has been discontinued for failure to meet milestones. All other projects had collaborative and milestone agreements put in place, and are achieving interim milestones and progressing according to schedules. Two projects adopted in FY11 (Duchenne Muscular Dystrophy; Fragile X Syndrome) have been discontinued from the TRND portfolio. The Duchenne Muscular Dystrophy partner is now able to carry out future steps without further TRND support, and the project is progressing according to schedules. Fragile X Syndrome was discontinued due to realignment of the collaborators business strategy. 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 supported development of novel technologies and collaborative paradigms that improve the efficiency of the translational process. For example, two projects represent 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. Holding meetings of the Trans-NIH Staff Advisory Group (TAG) to receive guidance and biological / disease area-specific insight during evaluation of solicited proposals. 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 refined TRND Research & Development Request for Proposals through which future research will be funded. 5. Evaluating and refining the solicitation and associated support system to bring new projects into the TRND pipeline.