The invention relates to tPA mutant devoid of protease activity and uses thereof in compositions and methods for the treatment and prevention of pathologic conditions involving neurological injury or an ischemic disease or condition. More specifically, the invention relates to a Ser481 to Ala mutant of tPA and to compositions and combinations thereof for the treatment of stroke, acute brain injury and neurodegenerative disorders. The invention further provides methods and kits for the treatment of said disorders.
