法国国家科研中心和普瓦提埃大学的研究人员日前宣布，他们发现一种名为美格鲁特的药物可有效治疗囊性纤维化。  

             
囊性纤维化是一种遗传性疾病，主要影响胃肠道和呼吸系统，通常具有慢性梗阻性肺部病变、胰腺外分泌功能不足和汗液电解质异常升高的特征，可威胁患者生命。  

研究人员在美国最新一期《呼吸细胞和分子生物学杂志》上报告说，他们发现，在病变细胞中注入美格鲁特后，在不停药的前提下可使病变细胞恢复正常。随后进行的小范围临床试验证实，囊性纤维化患者每天被注射小剂量的美格鲁特后，在两个月的治疗过程中，病人的各项参数逐渐恢复正常，不过一旦停药，他们的病情又会加重。
       
美格鲁特是一种葡萄糖苷酰鞘氨醇合成酶抑制剂，主要用于治疗另一种罕见的遗传性疾病——高雪氏病。

zavesca(Miglustat)治疗高雪病的首例药物由美国ACTELION 

PHARMS公司研制的治疗由葡萄糖酶脑苷脂酶出现功能性缺陷所引起的Ⅰ型高雪病的首例药物美格鲁特(Miglustat)胶囊剂以商品名zavesca
于2003年7月获得美国FDA批准。
                                     
高雪病为一种少见的疾病，由于葡萄糖酶脑苷脂酶出现功能性缺陷所致。此酶在人体内参与鞘糖脂葡萄糖鞘脑苷鞘氨醇的降解过程，当鞘糖脂葡萄糖鞘脑苷鞘氨醇的降解受到阻碍时，会使富含此种物质的巨嗜细胞的溶酶体在体内蓄积，发生广泛的病理反应，包括严重贫血、血小板减少、肝脾肿大、骨坏死和骨质减少。在治疗上常采用酶替代方法，美格鲁特用于无法以酶替代治疗的成年患者。
                                     
美格鲁特可降低鞘内糖脂的生物合成率，将葡萄糖苷鞘酶在人体内的浓度降至一个低水平，有助于改善Ⅰ型高雪病患者的肝、脾脏肿大，血色素、血小板计数低下的水平。推荐剂量为1次100mg，1日3次，若患者出现腹泻和震颤等不良反应，剂量可减少为1日1～2次；对轻度肾脏功能受损者(肌酐清除率为50～70ml/min /1.73m2)推荐剂量为1次100mg，1日2次；对轻度肾脏功能受损者(肌酐清除率为50～70ml/min  /1.73m2)推荐剂量为1次100mg，1日2次；对中度肾脏功能受损者(肌酐清除率为30～50ml/min /1.73m2)推荐剂量为1次100mg，1日1次；对重度肾脏功能受损者不宜应用。
                                     
其应用初始的第1个月，常见有震颤、腹泻、胃肠道不适、视力损害、体重减轻、麻木、疼痛、背痛、疲乏、手足烧灼感、肢体沉重、血小板减少等不良反应；对男性有可能影响精子的质量，因此在用药期间尽可能地采取避孕措施，对女性患者在服用期间建议不要怀孕。美格鲁特胶囊剂的规格为每粒100mg，每盒20粒。

Miglustat (Zavesca®)
Miglustat (Zavesca®) is a low-molecular-weight inhibitor of glucosylceramide synthase and α-glucosidase. Zavesca® (100 mg miglustat) is indicated for the oral treatment of adult patients with mild to moderate type 1 Gaucher disease, and may only be used in those patients for whom enzyme replacement therapy is unsuitable. It is approved for this indication in 37 countries including the US and EU since 2003. Zavesca® is also approved in the EU for the treatment of progressive neurological manifestations in adult and pediatric patients with Niemann-Pick type C disease.

Miglustat in type 1 Gaucher diseaseCurrent status
The MAINTENANCE trial is evaluating the long-term safety and efficacy of miglustat as maintenance therapy after a switch from enzyme replacement therapy (ERT) in mild-to-moderate adult type 1 Gaucher disease patients with stable disease. Enrollment in the MAINTENANCE trial was completed during the second quarter of 2008. Results of this study are expected to become available in 2010.
Available clinical data
Zavesca® (miglustat) 100 mg is the only oral drug available for the treatment of type 1 Gaucher disease, and was approved on the basis of three international open-label clinical trials. The rationale for the use of miglustat in type1Gaucherdisease is to help balance the overall level of glucosylceramide by reducing its production to a level compatible with breakdown by residual glucocerebrosidase activity, a unique mode of action known as "substrate reduction therapy". Bone manifestations of type 1 Gaucher disease were evaluated in three open-label clinical studies in patients treated with miglustat 100 mg t.i.d. for up to two years (n = 72). In a pooled analysis of uncontrolled data, bone mineral density Z-scores at the lumbar spine and femoral neck increased by more than 0.1 units from baseline in 27 (57%) and 28 (65%) of the patients with longitudinal bone density measurements. There were no events of bone crisis, avascular necrosis or fracture during the treatment period.

Milestones
2008 – EU approval for a type II variation for miglustat and bone disease in type 1 Gaucher disease
2008 – Zavesca® launched in Turkey and Brazil
2007 – Zavesca® approved in Australia
2005 – Zavesca® launched in Canada
2004 – Zavesca® launched in the US and Switzerland
2003 – Zavesca® launched in the EU
2002 – Zavesca® in-licensed; marketing authorization granted by European
CommissionKey scientific literaturePastores G.M. et al. Effect of miglustat on bone disease in adult patients with type 1 Gaucher disease: a pooled analysis of three multinational Open-label studies. Clinical Therapeutics. 29: 1645-53; 2007.

Elstein D. et al. Oral maintenance clinical trial with miglustat for type 1 Gaucher disease: switch from or combination with intravenous enzyme replacement. Blood. 110: 2296-2301; 2007.

Giraldo P. et al. Short-term effect of miglustat in every day clinical use in treatment-naïve or previously treated patients with type 1 Gaucher’s disease. Haematologica. 91:125-8; 2006.

Elstein D. et al. Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type 1 Gaucher disease.. J Inherit Metab Dis 27: 757-66; 2004.