The goal of this funding opportunity announcement (FOA) is to support preclinical development and testing of new therapies for neurological disorders. The program will facilitate therapy-directed projects to accelerate the translation of basic research discoveries into therapeutic candidates for clinical testing. Projects should include therapeutic leads, a strong biological rationale for the intended approach, and where available in vivo proof-of-concept of efficacy. The program supports preclinical optimization and testing of the leads, and projects must be sufficiently advanced that an Investigational New Drug (IND), Investigational Device Exemption (IDE), 510(k), or 510(k) de novo application to the Food and Drug Administration (FDA) can be submitted during the project period. The program can also support Phase 0 clinical trials for small molecule drugs, proof-of-concept for biologics, or proof-of-concept/pilot clinical trials for therapeutic devices. The program does not support early-stage therapeutic discovery activities such as screening. The program also excludes clinical research, other than those specified above, basic research, and studies of disease mechanism or mechanistic/mechanism of action studies of the intended therapeutic. The scope includes only therapy development activities, so development of diagnostics, biomarkers, or rehabilitation strategies cannot be supported. This is a milestone-driven cooperative agreement program involving participation of NINDS program staff in the development of the project plan and monitoring of research progress.