Gene Therapy Consortium (GTC) for Gene-Based Clinical Trials Conducted within NeuroNEXT - Abstract The long-term objective of the Network of Excellence in Neuroscience Clinical Trials (NeuroNEXT) initiative is to efficiently translate advances in neuroscience into treatments for adults and children with neurological disorders through partnerships with government, academia, private foundations, and industry. The goal of this proposal is to establish and operate a Gene Therapy Consortium (GTC) that provides expert advice on clinical trials of gene therapies for ultra-rare adult and pediatric disorders conducted within NeuroNEXT. The GTC will consist of members with expertise in gene-based and gene-targeted therapies, ultra-rare and rare diseases, and clinical trial planning and execution, with particular emphasis on first-in-human or first-in-disease trials, small clinical trials, and adaptive trial designs. The GTC will be organized and managed by the NeuroNEXT Clinical Coordination Center (CCC) and will provide advice as requested for gene therapy proposals. The GTC members will support investigators applying to NeuroNEXT in all phases starting at the conception and planning phases and continuing for funded proposals through implementation, analysis and reporting for gene therapy trials within NeuroNEXT. Ultra-rare diseases affect less than or equal to 6,000 people. Many rare diseases, including ultra-rare diseases, have no FDA-approved therapeutic available and have an identified genetic origin. The NINDS supports gene- based therapy research through the Ultra-Rare Gene-based Therapy (URGenT) program. NINDS announced that they will expand the URGenT program to support the conduct of gene-based therapy clinical trials for ultra rare neurological diseases. Gene therapy proposals will be submitted to the NINDS using the URGenT program synopsis form. NeuroNEXT will serve as a clinical trial network for the conduct of early clinical trials of gene therapy for ultra- rare pediatric and adult neurological disorders. NeuroNEXT is currently comprised of 13 clinical sites, a Clinical Coordinating Center (CCC), and a Data Coordinating Center (DCC). A central goal of NeuroNEXT is to facilitate, from initial conception through final analysis, high-quality early-phase clinical trials and biomarker multisite studies with clear go/no-go decisions by providing efficient methodological, organizational, statistical, and logistical support. Aim 1 is to establish a collaborative and accessible Gene Therapy Consortium (GTC) with members with diverse expertise to support investigators in developing and conducting gene-based and gene- targeted therapies trials within NeuroNEXT. Aim 2 is to establish and implement an efficient process for gene therapy proposals to move from concept to design, implementation, analysis and reporting, in collaboration with the NINDS NeuroNEXT program officials and the NeuroNEXT Data Coordination Center (DCC).
