The present invention provides methods and compositions for enhancing
recovery in a subject suffering from damage to the
nervous system. In particular, the invention includes a method for promoting
recovery and / or reorganization in the
nervous system of a subject in need of enhancement of
recovery and / or reorganization of the
nervous system as a result of ischemic, hemorrhagic, neoplastic, degenerative, or traumatic damage by focally administering a composition comprising a
proteolysis-enhancing agent such as
tissue plasminogen activator (tPA),
plasmin, or a PAI inhibitor to the nervous
system of the subject. In some embodiments an additional
active agent is also administered. The composition can be delivered using a variety of techniques including injection, via
infusion pump, from an implantable microchip, or using a polymeric
delivery vehicle. The composition can be administered, for example, to one or more subdivisions or areas of the brain, the
spinal cord, or to one or more nerves or nerve tracts innervating diverse regions of the body. The invention also includes a
drug delivery device for implantation into the nervous
system to promote nervous
system reorganization and / or recovery following ischemic, hemorrhagic, neoplastic, traumatic or degenerative damage, the
drug delivery device comprising a biocompatible
polymer and a
proteolysis-enhancing agent such as
tissue plasminogen activator (tPA),
plasmin, or a PAI inhibitor, wherein the
proteolysis-enhancing agent is released from the
polymer in an amount effective to promote structural reorganization of the nervous system. In some embodiments the biocompatible
polymer is a hydrogel.