Developing novel therapeutics for primary mitochondrial disease is likely to require significant academia‐industry collaboration. Translational assessments, a tool often used in industry at target validation stage, can highlight disease specific development challenges which requires focused collaborative effort. For PMD, definition of pivotal trial populations and primary endpoints is challenging given lack of clinical precedence, high numbers of subgroups with overlapping symptoms despite common genetics. Disease pathophysiology has not been systematically assessed simultaneously with outcomes in available natural history studies, resulting in a lack of pathophysiology biomarker utilization in clinical trials. Preclinical model systems are available to assist drug development efforts, although these may require better standardization and access. Multistakeholder precompetitive efforts have been used to progress disease pathophysiology biomarker and confirmatory clinical trial endpoint readiness in neurological disease with limited treatment options, such as rare familial Parkinson's disease. This type of approach may be beneficial for PMD therapeutic development, although requires significant funding and time, supported by industry and other funding bodies. Industry expertise on chemistry, data quality and drug development know‐how is available to support academic drug development efforts. A combination of industry mindset—reduction of uncertainty to provide an indication statement supportable by evidence—together with academic approach—question‐based studies to understand disease mechanisms and patients—has great potential to deliver novel PMD therapeutics.

中文翻译：

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合作开发针对原发性线粒体疾病的新疗法：工业界需要学术界提供什么，学术界需要工业界提供什么？

开发针对原发性线粒体疾病的新疗法可能需要大量的学术界和工业界合作。转化评估是工业中在目标验证阶段经常使用的一种工具，可以突出疾病特定的发展挑战，需要集中协作努力。对于 PMD，关键试验人群和主要终点的定义具有挑战性，因为缺乏临床优先性，尽管有共同的遗传学，但仍有大量具有重叠症状的亚组。疾病病理生理学尚未与现有自然史研究的结果同时进行系统评估，导致临床试验中缺乏病理生理学生物标志物的利用。临床前模型系统可用于协助药物开发工作，尽管这些可能需要更好的标准化和访问。多利益相关者的竞争前努力已被用于在治疗选择有限的神经系统疾病（例如罕见的家族性帕金森病）中推进疾病病理生理学生物标志物和确认性临床试验终点准备。这种类型的方法可能有利于 PMD 治疗的开发，尽管需要大量资金和时间，并得到行业和其他资助机构的支持。化学、数据质量和药物开发技术方面的行业专业知识可用于支持学术药物开发工作。行业思维——减少不确定性以提供有证据支持的适应症陈述——与学术方法——基于问题的研究以了解疾病机制和患者——相结合，具有提供新型 PMD 疗法的巨大潜力。