Composition and method to alter lean body mass and bone properties in a subject

Abstract

The present invention pertains to a method for decreasing the body fat proportion, increasing lean body mass (“LBM”), increasing bone density, or improving the rate of bone healing, or all, of a subject. Overall, the embodiments of the invention can be accomplished by delivering a heterologous nucleic acid sequence encoding GHRH or functional biological equivalent thereof into the cells of the subject and allowing expression of the encoded gene to occur while the modified cells are within the subject. For instance, when such a nucleic acid sequence is delivered into the specific cells of the subject tissue specific constitutive expression is achieved. Furthermore, external regulation of the GHRH or functional biological equivalent thereof gene can be accomplished by utilizing inducible promoters that are regulated by molecular switch molecules, which are given to the subject. The preferred method to deliver the constitutive or inducible nucleic acid encoding sequences of GHRH or the functional biological equivalents thereof is directly into the cells of the subject by the process of in vivo electroporation. A decrease the body fat proportion and an increase in lean body mass (“LBM”), or both of a subject is achieved by the delivery of GHRH or functional biological equivalent thereof as described herein by into the subject as recombinant proteins. In addition, an increase in bone density and improvement in the rate of bone healing is also achieved.

1 - 167 . (canceled) 
     
     
         168 . A peptide for altering bone density comprising a functional biological equivalent of growth hormone releasing hormone (“GHRH”), wherein the GHRH is a polypeptide that is biologically active in a subject; and the functional biological equivalent of GHRH is a polypeptide that has been engineered to contain distinct amino acid sequences while simultaneously having similar or improved biologically activity when compared to GHRH. 
     
     
         169 . The peptide of  claim 168  comprising the formula:
   -X 1 -X 2 -DAIFTNSYRKVL-X 3 -QLSARKLLQDI-X 4 -X 5 -RQQGERNQEQGA-OH   wherein the formula has the following characteristics:   X 1  is a D- or L-isomer of the amino acid tyrosine (“Y”), or histidine (“H”);   X 2  is a D- or L-isomer of the amino acid alanine (“A”), valine (“V”), or isoleucine (“I”);   X 3  is a D- or L-isomer of the amino acid alanine (“A”) or glycine (“G”);   X 4  is a D- or L-isomer of the amino acid methionine (“M”), or leucine (“L”);   X 5  is a D- or L-isomer of the amino acid serine (“S”) or asparagine (“N”); or a combination thereof.   
     
     
         170 . The peptide of  claim 168  comprising SeqID No: 1; SeqID No: 2; SeqID No: 3; or SeqID No: 4.