Sherman Merry R, Saifer Mark G P, Perez-Ruiz Fernando
Mountain View Pharmaceuticals, Inc., 3475-S Edison Way, Menlo Park, CA 94025, USA.
Adv Drug Deliv Rev. 2008 Jan 3;60(1):59-68. doi: 10.1016/j.addr.2007.06.011. Epub 2007 Aug 14.
Hyperuricemia results from an imbalance between the rates of production and excretion of uric acid. Longstanding hyperuricemia can lead to gout, which is characterized by the deposition of monosodium urate monohydrate crystals in the joints and periarticular structures. Because such deposits are resolved very slowly by lowering plasma urate with available drugs or other measures, the symptoms of gout may become chronic. Persistent hyperuricemia may also increase the risk of renal and cardiovascular diseases. Unlike most mammals, humans lack the enzyme uricase (urate oxidase) that catalyzes the oxidation of uric acid to a more soluble product. This review describes the development of a poly(ethylene glycol) (PEG) conjugate of recombinant porcine-like uricase with which a substantial and persistent reduction of plasma urate concentrations has been demonstrated in a Phase 2 clinical trial. Two ongoing Phase 3 clinical trials include systematic assessments of gout symptoms, tophus resolution and quality of life, in addition to the primary endpoint of reduced plasma urate concentration.
高尿酸血症是由尿酸生成和排泄速率失衡所致。长期的高尿酸血症可导致痛风，其特征是单水尿酸钠晶体沉积于关节和关节周围结构。由于通过现有药物或其他措施降低血浆尿酸水平后，此类沉积物的溶解非常缓慢，痛风症状可能会转为慢性。持续性高尿酸血症还可能增加肾脏疾病和心血管疾病的风险。与大多数哺乳动物不同，人类缺乏催化尿酸氧化为更易溶产物的尿酸酶（尿酸氧化酶）。本综述描述了重组猪样尿酸酶的聚乙二醇（PEG）缀合物的研发情况，在一项2期临床试验中已证明该缀合物可使血浆尿酸浓度大幅且持续降低。两项正在进行的3期临床试验除了将降低血浆尿酸浓度作为主要终点外，还包括对痛风症状、痛风石溶解情况和生活质量的系统评估。
