Long-Acting Growth Hormone Analogues

Growth hormone (GH) is an anabolic cytokine hormone regulating linear growth in childhood and normal body composition in adults. The current therapeutic regimen for GH replacement requires once-daily subcutaneous injections which is inconvenient and expensive. A number of approaches have been taken to create long-acting preparations, including depot preparations and sustained-release formulations. However, although of proven efficacy, such GH preparations are characterised by a dominant early-release profile, causing supraphysiological GH levels, manufacture is expensive and injections may be painful. There is a need for cytokine formulations that minimise manufacturing costs, have good pharmacokinetic profiles, are easy to administer, and are acceptable to patients. Recent focus has been on the generation of long-acting GH analogues by post-translational modification or protein fusions. In this article, we review the new technologies for generating long-acting GH agonists and GH antagonists including pegylation, albumin fusions and ligand-receptor fusions.