This Program Announcement with set-aside funds (PAS) invites applications proposing clinical and translational research in multiple sclerosis (MS) that target the neurodegenerative aspect of this disease. Applicants are expected to propose activities that are directly focused on the development of neuroprotective and regenerative therapies for MS. Applications in basic neuroscience or glial biology are not covered under this PAS. Applications for clinical trials and interventional studies are directed to use the funding mechanisms and opportunities listed at http://www.ninds.nih.gov/funding/clinical_trials/index.htm. The total amount to be awarded is up to $1,500,000 for the duration of this solicitation (3 years), in addition to funds available for applications sent in response to this program announcement that score within the NINDS payline. The number of individual awards will depend on the number and scientific merit of the applications received, as well as funds available. This PAS will use the NIH Research Project (R01) and Exploratory/Developmental Research (R21) award mechanisms. Eligible organizations include for-profit or non-profit domestic public or private institutions, units of state or local governments, eligible agencies of the Federal government, and foreign institutions.