Lentiviral-mediated growth factor gene therapy for nerodegenerative diseases

Abstract

Disclosed and claimed are methods for treating or preventing neurodegenerative diseases, conditions or maladies or symptoms or physiology associated therewith, such as treating or preventing Parkinson's disease or symptoms or physiology associated therewith such as motor deficits or nigrostriatal degeneration; or, for inducing nigrostriatal regeneration. Advantageously, the methods involve administering a lentiviral vector that expresses GDNF, such as human GDNF, or a variant, homolog, analog or derivative thereof.

1 . A method for treating or preventing a neurodegenerative disease, or symptoms thereof, in a mammal in need of such treatment comprising administering a lentiviral vector to a target cell in the nervous system of the mammal, said lentiviral vector comprising a nucleic acid sequence comprising a sequence encoding a growth factor operably linked to a promoter, wherein the growth factor is expressed in the target cell thereby treating or preventing said neurodegenerative disease.  
     
     
         2 . The method of  claim 1 , wherein the target cell is in the brain of the mammal.  
     
     
         3 . (Cancelled)  
     
     
         4 . (Cancelled)  
     
     
         5 . The method of  claim 1 , wherein the neurodegenerative disease is Parkinson's disease.  
     
     
         6 . (Cancelled)  
     
     
         7 . (Cancelled)  
     
     
         8 . (Cancelled)  
     
     
         9 . A method for treating or preventing nigrostriatal degeneration and/or inducing nigrostriatal regeneration in a mammal in need of such treatment comprising administering a lentiviral vector to a target cell in the nervous system of the mammal, said lentiviral vector comprising a nucleic acid sequence comprising a sequence encoding a growth factor operably linked to a promoter, wherein the growth factor is expressed in the target cell thereby treating or preventing said nigrostriatal degeneration and/or inducing nigrostriatal regeneration.  
     
     
         10 . The method of  claim 9 , wherein the target cell is in the brain of the mammal.  
     
     
         11 . The method of  claim 1 , wherein the lentiviral vector is an EIAV.  
     
     
         12 . The method of  claim 1 , wherein the lentiviral vector is an HIV.  
     
     
         13 . The method of  claim 1 , wherein the lentiviral vector is an SIV.  
     
     
         14 . The method of  claim 1 , wherein the lentiviral vector is an FIV.  
     
     
         15 . The method of  claim 1  wherein the lentiviral vector is a nonprimate lentiviral vector.  
     
     
         16 . The method of  claim 1 , wherein the nucleic acid sequence encodes a GDNF.  
     
     
         17 . The method of  claim 17 , wherein the GDNF is a human GDNF or a variant, homolog, analog or derivative of human GDNF that has activity of human GDNF.  
     
     
         18 . The method of  claim 18 , wherein the GDNF is a human GDNF.  
     
     
         19 . The method of  claim 1 , wherein the nervous system is the central nervous system.  
     
     
         20 . The method of  claim 1 , wherein the nervous system is the peripheral nervous system.  
     
     
         21 . The method of  claim 1 , wherein the mammal is a primate.  
     
     
         22 . The method of  claim 21  wherein the primate is a human.  
     
     
         23 . The method of  claim 1 , wherein the administering is intracranially.  
     
     
         24 . The method of  claim 23  wherein the administering intracranially is to the striatum.  
     
     
         25 . The method of  claim 23  wherein the administering intracranially is to the substantia nigra.  
     
     
         26 . The method of  claim 1 , wherein the administering is by retrograde transport.  
     
     
         27 . The method of  claim 1 , wherein there is growth factor expression for a duration of up to 8 months.  
     
     
         28 . The method of  claim 5 , wherein the treating of Parkinson's disease, or of symptoms thereof, is defined as a reversal of motor deficits.  
     
     
         29 . (Cancelled)  
     
     
         30 . (Cancelled)  
     
     
         31 . The method of  claim 9 , wherein the lentiviral vector is an EIAV.  
     
     
         32 . The method of  claim 9 , wherein the lentiviral vector is an HIV.  
     
     
         33 . The method of  claim 9 , wherein the lentiviral vector is an SIV.  
     
     
         34 . The method of  claim 9 , wherein the lentiviral vector is an FIV.  
     
     
         35 . The method of  claim 9 , wherein the lentiviral vector is a nonprimate lentiviral vector.  
     
     
         36 . The method of  claim 9 , wherein the nucleic acid sequence encodes a GDNF.  
     
     
         37 . The method of  claim 36 , wherein the GDNF is a human GDNF or a variant, homolog, analog or derivative of human GDNF that has activity of human GDNF.  
     
     
         38 . The method of  claim 37 , wherein the GDNF is a human GDNF.  
     
     
         39 . The method of  claim 9 , wherein the nervous system is the central nervous system.  
     
     
         40 . The method of  claim 9 , wherein the nervous system is the peripheral nervous system.  
     
     
         41 . The method of  claim 9 , wherein the mammal is a primate.  
     
     
         42 . The method of  claim 41 , wherein the primate is a human.  
     
     
         43 . The method of  claim 9 , wherein the administering is intracranially.  
     
     
         44 . The method of  claim 43  wherein the administering intracranially is to the stratum.  
     
     
         45 . The method of  claim 43  wherein the administering intracranially is to the substantia nigra.  
     
     
         46 . The method of  claim 9 , wherein the administering is by retrograde transport.  
     
     
         47 . The method of  claim 9 , wherein there is growth factor expression for a duration of up to 8 months.