Disseminating Curative Biological Therapies for Rare Pediatric Diseases

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Project Summary/Abstract Gene and cell therapies, especially for rare diseases, require complex product-specific development of pre- clinical studies, costly GMP manufacturing, unique laboratory assays for monitoring, and extraordinary regulatory management to initiate, perform and oversee clinical trials that provide initial assessments of safety and efficacy. Due to the rarity of many serious and life-threatening genetic diseases in the pediatric population, an increasing number of which may be curable using emerging gene and cell therapy approaches, a significant barrier to translation of these innovative therapies and future gene editing approaches is the limited number of institutions with infrastructure to carry out these developmental steps and the complex regulatory environment involving biologicals and early phase human studies in children. This is particularly true in pediatric rare genetic diseases where no one center cares for sufficient numbers of patients to successfully carry out robust prospective trials. This set of circumstances leads to significant problems: 1) families displaced from their jobs and support structures due to lengthy relocation to participate in trials centered at sites at significant distances from their homes; 2) decisions not to participate in trials due to the lack of financial and social structures created by these displacements; 3) slow accrual to trials in spite of eligible patients. Given the recent early successes of gene transfer methods and the expanding knowledge of the genetic basis of diseases, these novel therapeutic approaches may increasingly be sought by disease experts who lack detailed knowledge of the complex translational pathway involved. Many of these experts are in research/medical centers that have not developed the costly infrastructure to efficiently move the gene transfer research to the clinic, much less to develop a multi-site clinical trial likely to recruit adequate numbers of subjects. A second impediment to efficient translation of these highly regulated trials is the time required to navigate multiple regulatory structures, in particular, reviews by multiple Institutional Review Boards (IRBs) with little experience in the complexities of gene therapy trials. We propose to develop a network of pediatric centers with unique expertise and experience in translation of gene therapies. Our overall goal is to support investigators across multiple CTSAs to more rapidly translate complex gene therapies to early phase investigator-initiated pediatric clinical trials suitable for transfer to industry. The centers participating in this U01 would then be well positioned to apply for clinical trial funding and to enter into agreements with industry sponsors. The Disseminating Curative Biological Therapies for Rare Pediatric Diseases Collaborative Consortium will offer key services and expert advice in order to enhance enrollment on gene therapy clinical trials nationally.