Recombinant human GHRH(1-44)NH2: clinical utility and therapeutic development program.

Growth hormone (GH) secretagogues are becoming increasingly attractive alternatives to GH or insulin-like growth factor-I (IGF-I) for the treatment of conditions that may benefit from activation of the GH/IGF-I axis. This stems from the realization that (1) GH secretagogues stimulate the pulsatile release of endogenous GH; (2) feedback control of endogenous GH and IGF-I is preserved, guarding against imbalances between GH and IGF-I levels; and (3) GH treatment is associated with adverse effects in the elderly. Of the GH secretagogues, growth hormone-releasing hormone (GHRH) remains the best characterized, in terms of identity of the ligand-receptor pair and its exclusive somatotropic activity at the level of the pituitary. Full-length natural GHRH (1-44) amide can now be produced by recombinant technologly on a commercially viable scale, and is currently being evaluated in early phase clinical trials. The purpose of these studies is to evaluate the efficacy and tolerability of chronic subcutaneous administration of GHRH over a range of doses in elderly subjects. Therapeutic areas that are being investigated in the elderly include congestive heart failure, osteoporosis, and improvements in body composition and function in the frail elderly.