BMP-1 Procollagen C-Proteinase for Diagnosis and Treatment of Bone and Soft Tissue Defects and Disorders

Abstract

Uses of BMP-1 isoforms for diagnosing and treating defects and disorders of bone and soft tissues are described. Also described is a newly isolated variant of the BMP-1 isoform BMP-1-3.

1 . A method of treating ischemic acute renal failure in an individual comprising administering a BMP-1 isoform systemically to the individual after diagnosis of renal injury. 
     
     
         2 . A method of treating an individual for a defect or disorder in bone or soft tissue of an individual comprising:
 (a) diagnosing a defect or disorder in a bone or soft tissue in an individual by steps comprising:
 (i) determining the profile of BMP-1 isoforms in the blood and 
 (ii) comparing the profile to a standard blood profile of BMP-1 isoforms associated with various defects and disorders, 
   (b) administering to the individual an amount of at least one BMP-1 isoform effective to enhance the therapeutic effect of an osteogenic BMP toward the diagnosed defect or disorder, or administering to the individual an amount of one or more antibody molecules specific for one or more BMP-1 isoforms effective to inhibit the effects of said one or more BMP-1 isoforms in the progression of the diagnosed defect or disorder.   
     
     
         3 . The method according to  claim 2 , wherein said standard blood profile of BMP-1 isoforms is Table 1. 
     
     
         4 . The method according to  claim 2 , wherein said soft tissue is in a parenchyma organ. 
     
     
         5 . The method according to  claim 4 , wherein said parenchyma organ is selected from the group consisting of liver, pancreas, and kidney. 
     
     
         6 . The method according to  claim 2 , wherein in step (b) a BMP-1 isoform is administered to the individual systemically or locally at a site of the defect or disorder. 
     
     
         7 . The method according to  claim 2 , wherein in step (b) an antibody to a BMP-1 isoform is administered systemically. 
     
     
         8 . The method according to  claim 2 , wherein said BMP-1 isoform or said antibody molecule is administered systemically via intravenous or intramuscular injection. 
     
     
         9 . A method of pretreating an individual to resolve clots that may occur during thoracic or abdominal surgery comprising administering a BMP-1 isoform to the individual prior to surgery in an amount effective to inhibit the occurrence of clots. 
     
     
         10 . A method of treating acute pancreatitis in an individual comprising administering to the individual a therapeutically effective amount of at least one antibody molecule specific for a BMP-1 isoform. 
     
     
         11 . The method according to  claim 10 , wherein the antibody molecule is an anti-BMP-1-7 antibody molecule. 
     
     
         12 . A method of treating pancreatitis in an individual comprising administering to an individual suffering from pancreatitis, after the acute phase of the inflammatory process, an amount of a BMP-1 isoform in an amount effective to promote pancreatic regeneration. 
     
     
         13 . The method according to  claim 12 , wherein the BMP-1 isoform administered is BMP-1-7. 
     
     
         14 . An osteogenic whole blood-derived coagulum device (WBCD) for treating a bone defect in an individual prepared by the steps comprising:
 (a) preparing a mixture comprising:
 (1) whole blood, 
 (2) a BMP-1 isoform, 
 (3) an exogenous substance supplying calcium ions, and 
 (4) optionally, a mixture of fibrin and thrombin, and 
 (5) optionally, an osteogenic BMP; 
   (b) incubating the mixture of step (a) until a mechanically stable gel is formed, wherein said mechanically stable gel is a homogenous, cohesive, syringeable, injectable, and malleable coagulum gel.   
     
     
         15 . The osteogenic WBCD according to  claim 14 , wherein the whole blood is autologous whole blood drawn from the individual or is whole blood that has been crossmatched with the individual. 
     
     
         16 . The osteogenic WBCD according to  claim 14 , wherein step (a) is carried out by first combining the fibrin-thrombin mixture, calcium ion substance, and the BMP-1 isoform to form a first mixture, adding whole blood to the first mixture to form a second mixture, and incubating the second mixture until a mechanically stable gel is formed. 
     
     
         17 . A method of treating a bone defect in an individual comprising administering the WBCD according to  claim 14  to the bone defect. 
     
     
         18 . The method according to  claim 17 , wherein the WBCD is administered by implantation or by injection into the bone defect. 
     
     
         19 . A kit for preparing an osteogenic whole blood-derived coagulum device (WBCD) comprising:
 (a) a vial containing one or more lyophilized BMP-1 isoform,   (b) a buffer for reconstituting the lyophilized BMP-1 isoforms(s),   (c) a syringe for reconstituting the lyophilized BMP-1 isoform(s) in the buffer,   (d) a vaccutainer for collecting a patient's blood,   (e) a sterile solution of 1 M calcium chloride,   (f) a fibrin-thrombin mixture,   (g) a container for mixing whole blood with the reconstituted BMP-1 isoform(s) and other ingredients,   (h) a spatula or syringe suitable for applying an osteogenic coagulum to bone ends during open bone repair surgery, and   (i) instructions for the preparation and use of a WBCD comprised of whole blood mixed with one or more BMP-1 isoforms, calcium chloride and, optionally, a mixture comprising fibrin and thrombin, to form a mechanically stable gel suitable for application to a bone defect, wherein said mechanically stable gel is a homogenous, cohesive, syringeable, injectable, and malleable coagulum gel.   
     
     
         20 . An isolated BMP-1 isoform having the amino acid sequence of SEQ ID NO:4. 
     
     
         21 . An isolated polynucleotide encoding the polypeptide having the amino acid sequence of SEQ ID NO:4. 
     
     
         22 . The polynucleotide according to  claim 21  having the nucleotide sequence of SEQ ID NO:5.