Gene therapy for diabetic neuropathy using an hgf isoform

Abstract

The present invention relates to a pharmaceutical composition for the prevention or treatment of diabetic neuropathy, wherein the pharmaceutical composition comprises, as active ingredients, different types of isoforms of HGF or a polynucleotide encoding the isoforms. The present invention is the first invention demonstrating that diabetic neuropathy can be prevented and treated using different types of isoforms of HGF. According to the present invention, it is possible to very effectively treat diabetic neuropathy.

1 . A method for treating a human subject having painful diabetic peripheral neuropathy, the method comprising:
 intramuscularly administering to an affected limb of the human subject in need thereof a pCK-HGF-X7 DNA construct at a dose of 8 mg per affected limb, divided into a plurality of pain-tolerable injections,   wherein the pCK-HGF-X7 DNA construct comprises the nucleotide sequence as set forth in SEQ ID NO: 13.   
     
     
         2 . The method of  claim 1 , wherein the step of intramuscularly administering the DNA construct at a dose of 8 mg per affected limb is done over two visits. 
     
     
         3 . The method of  claim 2 , wherein the step of intramuscularly administering the DNA construct at a dose of 8 mg per affected limb is performed on both legs of the human subject. 
     
     
         4 . The method of  claim 2 , wherein the step of intramuscularly administering an 8 mg dose comprises (i) administering 4 mg of the DNA construct to the affected limb divided into 16 pain-tolerable injections on a first visit, and (ii) administering 4 mg of the DNA construct to the affected limb divided into 16 pain-tolerable injections on a second visit. 
     
     
         5 . The method of  claim 4 , further comprising repeating the step of intramuscularly administering an 8 mg dose in a subsequent plurality of visits. 
     
     
         6 . The method of  claim 5 , wherein the step of repeating comprises (i) administering 4 mg of the DNA construct divided into 16 pain-tolerable injections on a third visit, and (ii) administering 4 mg of the DNA construct divided into 16 pain-tolerable injections on a fourth visit. 
     
     
         7 . A method for treating a human subject having painful diabetic peripheral neuropathy, the method comprising:
 intramuscularly administering to an affected limb of the human subject in need thereof a pCK-HGF-X7 DNA construct at a dose of 4 mg per affected limb, divided into 16 pain-tolerable injections on a first visit;   intramuscularly administering to the affected limb the pCK-HGF-X7 DNA construct at a dose of 4 mg per affected limb, divided into 16 pain-tolerable injections on a second visit;   intramuscularly administering to the affected limb the pCK-HGF-X7 DNA construct at a dose of 4 mg per affected limb, divided into 16 pain-tolerable injections on a third visit; and   intramuscularly administering to the affected limb, the pCK-HGF-X7 DNA construct at a dose of 4 mg per affected limb, divided into 16 pain-tolerable injections on a fourth visit,   wherein the pCK-HGF-X7 DNA construct comprises the nucleotide sequence as set forth in SEQ ID NO: 13.