PAR : Clinical Trial Readiness for Rare Neurological and Neuromuscular Diseases Clinical Trial Readiness Validated biomarkers and clinical outcome measures, knowledge of disease course, effective recruitment strategies Candidate Therapeutics Supported through OTR and other sources Clinical Trials Clinical Research Infrastructure Supported through NeuroNEXT or other networks Goals of this new initiative: To acquire knowledge and refine tools that facilitate design of upcoming trials To develop accurate, sensitive and reliable biomarkers and outcome measures that enable future trials to be well-powered and shorter in duration To characterize clinical cohorts and test recruitment strategies that will increase the likelihood of successful trials

Description of the Initiative Types of studies that would be supported through this initiative: Rare neurological or neuromuscular diseases (<200,000 pts in US) Needed to facilitate one or more upcoming trials Aims may include:  Biomarker or clinical outcome measure validation/qualification  Patient cohort characterization  Testing of recruitment strategies through above studies  Newly recruited participants or ancillary to an ongoing clinical trial Types of studies that would be outside the scope of this initiative: Natural history studies without direct relevance to upcoming trials Biomarker discovery, pathophysiology or GWAS studies Support for establishing clinical research infrastructure or patient registries

Specialized peer review administered by NINDS: Attention to significance for that rare disease, unmet need and urgency in relation to ongoing therapy development efforts Reviewer expertise on rare neurological diseases, biomarker/outcome measure validation, multi-site clinical data management and biostatistics Milestones for enrollment targets and biomarker/outcome measure performance evaluated by reviewers and throughout life of the grant by program Success in this initiative would lead to increased success in future clinical trials for rare neurological and neuromuscular diseases. Description of the Initiative (continued)

RD CT Readiness Working Group Channels Synapses and Circuits Brandy Fureman Vicky Whittemore Neural Environment Jane Fountain Ursula Utz Neurodegeneration Amelie Gubitz Margaret Sutherland Neurogenetics Katrina Gwinn Laura Mamounas Jill Morris Ashlee Van’t Veer Office of Translational Research Hao Wang Office of Clinical Research Elizabeth McNeil Patricia Walicke