Administration of growth factors for the treatment of cns disorders

Abstract

A method and system that is directed to the local delivery of growth factors to the mammalian CNS to treat CNS disorders associated with neuronal death and/or dysfunction is described.

1 - 15 . (canceled) 
     
     
         16 . A method of treating a human patient having a central nervous system disease, the method comprising administering to a target brain tissue of said patient a therapeutically effective amount of a pharmaceutical composition comprising a growth factor, wherein
 said growth factor is administered by intermittent convection enhanced delivery (CED) at a rate that counters the tissue clearance rate of said growth factor,   there is cessation of growth factor delivery during the intermissions between administrations,   the intermissions between administration of said growth factor are at least about one week, and   said therapeutically effective amount is an amount effective to increase neurotransmitter turnover in growth factor-responsive neurons of the mammalian CNS.   
     
     
         17 . A method of treating a human patient having a central nervous system disease, the method comprising administering to a target brain tissue of said patient a therapeutically effective amount of a pharmaceutical composition comprising a growth factor, wherein
 said growth factor is administered by intermittent convection enhanced delivery (CED) at a rate that counters the tissue clearance rate of said growth factor,   there is cessation of growth factor delivery during the intermissions between administrations,   the intermissions between administration of said growth factor are at least about one week, and   said therapeutically effective amount is an amount effective to modulate synapse formation by growth factor-responsive neurons of the mammalian CNS.   
     
     
         18 . A method of treating a human patient having a central nervous system disease, the method comprising administering to a target brain tissue of said patient a therapeutically effective amount of a pharmaceutical composition comprising a growth factor, wherein
 said growth factor is administered by intermittent convection enhanced delivery (CED) at a rate that counters the tissue clearance rate of said growth factor,   there is cessation of growth factor delivery during the intermissions between administrations,   the intermissions between administration of said growth factor are at least about one week, and   said therapeutically effective amount is an amount effective to modulate neurite outgrowth by growth factor-responsive neurons of the mammalian CNS.   
     
     
         19 . The method according to  claim 16 ,  17  or  18 , wherein said pharmaceutical composition further comprises a tracing agent. 
     
     
         20 . The method according to  claim 16 ,  17  or  18 , wherein said CED comprises incremental increases in flow rate. 
     
     
         21 . The method according to  claim 16 ,  17  or  18 , wherein the pharmaceutical composition is delivered with the use of a CED-compatible reflux-free step-design cannula. 
     
     
         22 . The method according to  claim 19 , wherein the tracing agent comprises an MRI magnet or a CT-detectable agent. 
     
     
         23 . The method according to  claim 19 , wherein said tracing agent comprises a liposome. 
     
     
         24 . The method according to  claim 19 , wherein said tracing agent is a gadolinium chelate. 
     
     
         25 . The method according to  claim 16 ,  17  or  18 , wherein said pharmaceutical composition comprises a high molecular weight neurotherapeutic comprising said growth factor. 
     
     
         26 . The method according to  claim 16 ,  17  or  18 , wherein said pharmaceutical composition further comprises low molecular weight heparin as a facilitating agent. 
     
     
         27 . The method according to  claim 16 ,  17  or  18 , wherein said growth factor is selected from the group consisting of NGF, BDNF, NT-3, NT-4/5, NT-6, GDNF, CNTF, LIF, IGF-1, bFGF, neurturin, persephin, artemin, TGFα, TGFβ, IGF-2, PDGF, EGF, IGF, BMP, FGF20, VIP, pleiotrophin (PTN), and HGF. 
     
     
         28 . The method according to  claim 16 ,  17  or  18 , wherein the intermissions between administrations of said growth factor are between about 7 and 45 days. 
     
     
         29 . The method according to  claim 16 ,  17  or  18 , wherein cessation of delivery occurs when infusate is distributed throughout the substantial whole of the target brain tissue. 
     
     
         30 . The method according to  claim 16 ,  17  or  18 , wherein cessation of delivery occurs while infusate remains substantially confined to the target brain tissue. 
     
     
         31 . The method according to  claim 16 ,  17  or  18 , comprising three or more administrations, wherein the durations of two or more intermissions are varied in length of time. 
     
     
         32 . The method according to  claim 16 ,  17  or  18 , wherein the duration of intermissions increases over time. 
     
     
         33 . The method according to  claim 16 ,  17  or  18 , wherein the method comprises administering to a target tissue selected from the group consisting of striatum, putamen, caudate nucleus, substantia nigra, basal forebrain, midbrain, nucleus basalis of Meynert, and hippocampus of said patient, or a combination thereof.