Administration of polypeptide growth factors following central nervous system ischemia or trauma

Abstract

The present invention relates to the treatment of central nervous system injuries by intracisternal or intravenous administration of polypeptide growth factors, such as basic fibroblast growth factor. This method provides significant benefits because administration can occur a substantial amount of time following an injury.

What is claimed is:  
     
         1 . A method for treating a patient who has suffered an injury to the central nervous system, the method comprising administering to the patient a polypeptide growth factor, the administration occurring more than six hours after the onset of the injury.  
     
     
         2 . The method of    claim 1   , wherein said injury comprises an ischemic episode.  
     
     
         3 . The method of    claim 1   , wherein said injury is a traumatic injury.  
     
     
         4 . The method of    claim 1   , wherein said polypeptide growth factor is a fibroblast growth factor (FGF).  
     
     
         5 . The method of    claim 4   , wherein said fibroblast growth factor is basic FGF (bFGF), acidic FGF (aFGF), the hst/Kfgf gene product, FGF-5, int-2, or active fragments thereof.  
     
     
         6 . The method of    claim 1   , wherein said polypeptide growth factor is a neurotrophin.  
     
     
         7 . The method of    claim 6   , wherein said neurotrophin is nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), or neurotrophin 4/5 (NT4/5), or active fragments thereof.  
     
     
         8 . The method of    claim 1   , wherein said polypeptide growth factor is ciliary neurotrophic growth factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M, or an interleukin.  
     
     
         9 . The method of    claim 1   , wherein said polypeptide growth factor is administered according to a treatment regimen, including dosage, mode of administration, and timing of administration, that is sufficient to improve functional recovery in said patient from the adverse consequences of the injury.  
     
     
         10 . The method of    claim 9   , wherein said functional recovery comprises an improvement in at least one of said patient's (a) motor skills, (b) cognitive skills, (c) sensory perceptions, and (d) speech.  
     
     
         11 . The method of    claim 9   , wherein said treatment regimen occurs more than 12 hours after said ischemic episode.  
     
     
         12 . The method of    claim 9   , wherein said treatment regimen occurs more than 24 hours after said ischemic episode.  
     
     
         13 . The method of    claim 9   , wherein said treatment regimen occurs more than 48 hours after said ischemic episode.  
     
     
         14 . The method of    claim 9   , wherein said treatment regimen comprises intravenous administration.  
     
     
         15 . The method of    claim 14   , wherein said intravenous administration comprises administration of 10 to 1,000 μg/kg of a polypeptide growth factor.  
     
     
         16 . The method of    claim 9   , wherein said treatment regimen comprises intracerebral administration.  
     
     
         17 . The method of    claim 16   , wherein said intracerebral administration is intracisternal.  
     
     
         18 . The method of    claim 17   , wherein said intracisternal administration comprises administration of a single injection of approximately 0.1 to 100 μg/kg/injection.  
     
     
         19 . The method of    claim 18   , wherein said administration occurs approximately 24 hours after said injury to the central nervous system.  
     
     
         20 . The method of    claim 17   , wherein said intracisternal administration comprises administration of a series of injections of approximately 1.5 to 3.0 μg/kg/injection.  
     
     
         21 . The method of    claim 20   , wherein said administration occurs biweekly.  
     
     
         22 . The method of    claim 20   , wherein said administration occurs approximately 24 hours after said injury to the central nervous system.  
     
     
         23 . The method of    claim 2   , wherein said ischemic episode is global cerebral ischemia.  
     
     
         24 . The method of    claim 2   , wherein said ischemic episode is focal cerebral ischemia.  
     
     
         25 . The method of    claim 2   , wherein said ischemic episode is caused by hypertension, hypertensive cerebral vascular disease, rupture of an aneurysm, an embolus, a thrombus, an angioma, blood dyscrasias, cardiac failure, systemic hypotension, cardiac arrest, cardiogenic shock, septic shock, spinal cord trauma, head trauma, seizure, bleeding from a tumor, or other blood loss.  
     
     
         26 . The method of    claim 1   , wherein said treatment regimen causes acceleration of new neuronal sprouting and synapse formation within the central nervous system.  
     
     
         27 . The method of    claim 1   , wherein said treatment regimen inhibits retrograde neuronal death within the central nervous system.  
     
     
         28 . The method of    claim 9   , wherein said treatment regimen comprises intrathecal administration.