Method for treating diabetic ulcers

Abstract

A method and means have been developed to deliver a therapeutic dose or dosages of the angiogenic molecule, Vascular Endothelial Growth Factor (VEGF) that results in a statically significant decrease in the time to achieve 100% wound closure and accelerates the rate of healing in experimental diabetic ulcers. Toxicity is evaluated by measuring any local inflammatory response at the wound site, the systemic absorption of VEGF, and the effect on distant organs that may be particularly susceptible to VEGF therapy (e.g., retinopathy and hepatitis) The angiogenic response is quantified by measuring the change in collagen deposition, epithelialization, and the closure rates of diabetic ulcers after therapeutic dosing with ADV-VEGF. Sustained administration of VEGF stimulates and accelerates the healing process as evidenced by a reduced time to complete healing (defined by 100% epithelialization and no drainage) in experimental diabetic ulcers, with minimal to no toxicity. Important features of the method and reagents for use therein are that the VEGF is released into the ulcer in a sufficient quantity over a period of time for at least two to six weeks, or to closure of the wound.

I claim:  
     
         1 . A method for tissue engineering a diabetic ulcer comprising administering to the wound an effective amount of VEGF for a sustained period of time of at least two weeks to enhance the rate of closure of the wound.  
     
     
         2 . The method of  claim 1  wherein the VEGF is administered in the form of a nucleic acid molecule encoding the VEGF.  
     
     
         3 . The method of  claim 1  wherein the VEGF reverses bacterial contamination of the wound in a patient with a diabetic ulcer.  
     
     
         4 . The method of  claim 2  wherein the nucleic acid molecule is a viral vector.  
     
     
         5 . The method of  claim 4  further comprising administering the adenoviral vector at a concentration of at least 1.6×10 10  adenoviral-VEGF particles.  
     
     
         6 . The method of  claim 4  further comprising administering the adenoviral vector at a concentration of at least 5×10 10  adenoviral-VEGF particles.  
     
     
         7 . The method of  claim 4  further comprising administering the adenoviral vector at a concentration of at least 5×10 11  adenoviral-VEGF particles.  
     
     
         8 . The method of  claim 2  wherein the nucleic acid molecule is in the form of genetically engineered cells secreting VEGF.  
     
     
         9 . The method of  claim 2  wherein the nucleic acid molecule is in the form of naked DNA encoding VEGF.  
     
     
         10 . The method of  claim 1  wherein the VEGF is administered by a sustained delivery pump.  
     
     
         11 . The method of  claim 1  wherein the VEGF is administered in a sustained delivery polymeric device.  
     
     
         12 . The method of  claim 8  wherein the device is formed of a biodegradable polymer in the form of microspheres, slabs, disks, or gels.  
     
     
         13 . The method of  claim 1  wherein the VEGF is released over a period of between two and six weeks.  
     
     
         14 . A composition for tissue engineering a diabetic ulcer comprising an effective amount of VEGF administered for a sustained period of time of at least two weeks to enhance the rate of closure of the wound.  
     
     
         15 . The composition of  claim 14  wherein the VEGF is in the form of a nucleic acid molecule encoding the VEGF.  
     
     
         16 . The composition of  claim 14  wherein the VEGF is in the form of a viral vector encoding the VEGF.  
     
     
         17 . The composition of  claim 15  wherein the nucleic acid molecule is in the form of genetically engineered cells secreting VEGF.  
     
     
         18 . The composition of  claim 15  wherein the nucleic acid molecule is in the form of naked DNA encoding VEGF.  
     
     
         19 . The composition of  claim 14  wherein the VEGF is formulated in a sustained delivery pump.  
     
     
         20 . The composition of  claim 14  wherein the VEGF is formulated in a sustained delivery polymeric device.  
     
     
         21 . The composition of  claim 20  wherein the device is formed of a biodegradable polymer in the form of microspheres, slabs, disks, or gels.