Parkinson C, Scarlett J A, Trainer P J
Department of Endocrinology, Christie Hosptial, Wilmslow Road, Manchester M20 4BX, UK.
Adv Drug Deliv Rev. 2003 Sep 26;55(10):1303-14. doi: 10.1016/s0169-409x(03)00111-x.
Epidemiological studies have highlighted the need for tight control of growth hormone (GH) and insulin-like growth factor I (IGF-I) in patients with acromegaly. Studies highlighting the events involved in GH receptor signaling have allowed the development of a pegylated GH receptor antagonist (pegvisomant) for use in humans, which has been designed to outcompete GH for the GH receptor, but which contains a position 120 amino acid substitution that prevents recruitment of a second GH receptor. This process of receptor dimerisation is crucial for signal transduction and IGF-I generation. Clinical trials of pegvisomant suggest it is the most effective treatment for acromegaly to date, as this therapy is capable of normalising serum IGF-I in up to 97% of patients when doses of 40 mg per day are used. This paper reviews the development of pegvisomant and the clinical experience in patients with acromegaly to date.
流行病学研究强调了对肢端肥大症患者严格控制生长激素（GH）和胰岛素样生长因子I（IGF-I）的必要性。对GH受体信号传导相关事件的研究促使了一种聚乙二醇化GH受体拮抗剂（培维索孟）的研发，该拮抗剂可供人类使用，其设计目的是在GH受体上与GH竞争，但含有第120位氨基酸替代，可阻止第二个GH受体的募集。这种受体二聚化过程对于信号转导和IGF-I生成至关重要。培维索孟的临床试验表明，它是迄今为止治疗肢端肥大症最有效的方法，因为当每天使用40毫克剂量时，这种疗法能够使高达97%的患者血清IGF-I恢复正常。本文综述了培维索孟的研发情况以及迄今为止肢端肥大症患者的临床经验。
