Clinical use of a growth hormone receptor antagonist in the treatment of acromegaly.
Drake, William M Parkinson, Craig Besser, G M Trainer, Peter J
Drake, William M
Parkinson, Craig
Besser, G M
Trainer, Peter J
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Abstract
The elucidation of the mechanisms by which growth hormone (GH) interacts with its receptor has facilitated the design of compounds that function as GH-receptor antagonists. One such compound, B2036, has been conjugated to polyethylene glycol to produce a drug, pegvisomant, that has a powerful ability to lower circulating concentrations of insulin-like growth factor I (IGF-I), the principal mediator of GH action, in patients with acromegaly and to improve the symptoms and signs associated with GH excess. This article describes the mechanism of action of GH-receptor antagonists, reviews the preclinical and clinical data on the use of pegvisomant and discusses some of the challenges that lie ahead in judging the efficacy of a treatment that, unlike established therapies for acromegaly, does not aim to modify the underlying cause of acromegaly, namely excess GH secretion, but aims to lower serum IGF-I levels to normal.
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2001-11
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Clinical use of a growth hormone receptor antagonist in the treatment of acromegaly. 2001, 12 (9):408-13 Trends Endocrinol. Metab.