PEGylation of human growth hormone: strategies and properties

Abstract

Recombinant human growth hormone (hGH) is a well characterized molecule with broad acceptance as a treatment for growth hormone deficiencies (GHD). However, treatment with hGH requires daily injections due to the drug's short duration of action. Many groups have focused on PEGylation of hGH as a means to extend its half-life and generate less frequent dosage forms. This chapter provides a review of the preclinical and clinical results obtained from the many approaches directed towards modification of hGH with PEG. The chapter will describe a historical progression of PEGylation strategies and results. The first half of the chapter will discuss initial studies that utilized multiple 5 kDa PEG attachments for extension of hGH half-life and the subsequent development of a PEGylated hGH receptor antagonist, pegvisomant, a successful therapy for acromegaly. The latter half of the chapter will summarize more recent and current work focusing on site selective mono-PEGylation of hGH.