Genet in Med：抗癌药物或可助力庞贝氏症患者的治疗

通过将抗癌药物与当前疗法的药物混合可以使得患有严重庞贝氏症的婴儿疾病得到明显的缓解甚至治愈，庞贝氏症是一种罕见的致死性的遗传病，其主要表现为婴儿机体的某种酶类缺少或者水平极低，导致婴儿死亡。此前研究中，来自杜克大学的研究者使用酶替代疗法（ERT）来治疗庞贝氏症，这项新的研究中，研究者对此前的疗法进行了改进和补充，相关研究成果刊登在了10月11日的国际杂志Genetics in Medicine上。

某些庞贝氏症婴儿由于机体存在多种的突变组合，因此很容易表现出对ERT疗法的耐受性，此前的研究中，研究者仅仅使用含有低剂量的抗癌药物利妥昔单抗和甲氨蝶呤，加上免疫促进剂丙种球蛋白来抑制患者对ERT产生耐药，而且效果比较明显。

使用上述三种药物确实可以使得患者对ERT的耐药性得到明显改善，但是随着患者机体内出现了高水平的抗体，其会抑制酶的替代疗法，在婴儿机体中，浆细胞，其是抗体最终产生的来源，其并不会被免疫抑制药物制剂所影响和抑制。

在这项最新研究中，研究者将一种蛋白酶体抑制剂-硼替佐米添加到原来的治疗药物中，硼替佐米是FDA批准的用于治疗多发性骨髓瘤和外套细胞淋巴瘤的药物，其以浆细胞为靶点来抑制抗体的产生，从而逆转已经建立的免疫反应。

研究者Suhrad Banugaria表示，添加硼替佐米后所得到的临床效果非常鼓舞人心，我们很快将会开发出使用硼替佐米来治疗患者的临床疗法和步骤，下一步，我们将以特异性的抗原来引出对ERT耐药的免疫系统，从而继续深入研究，开发出对免疫系统副作用最小的新型疗法。

与抗癌相关的拓展阅读：

• Sci Signal：抗癌药物或可用于治疗肌肉变性疾病
• Nature Medicine:新的肠癌亚类型对抗癌药物具有更强耐受性
• JCEM：Beclin1具有独立于自噬的抗癌效应
• H7N9：禽流感病毒可抗癌细胞
• 新型化疗药物保育抗癌双管齐下 更多信息请点击：有关抗癌更多资讯

Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease

Purpose: High sustained antibody titers complicate many disorders treated with a therapeutic protein, including those treated with enzyme replacement therapy, such as Pompe disease. Although enzyme replacement therapy with alglucosidase alfa (Myozyme) in Pompe disease has improved the prognosis of this otherwise lethal disorder, patients who develop high sustained antibody titers to alglucosidase alfa enter a prolonged phase of clinical decline resulting in death despite continued enzyme replacement therapy. Clinically effective immune-tolerance induction strategies have yet to be described in the setting of an entrenched immune response characterized by high sustained antibody titers, wherein antibody-producing plasma cells play an especially prominent role. Methods: We treated three patients with infantile Pompe disease experiencing marked clinical decline due to high sustained antibody titers. To target the plasma cell source of high sustained antibody titers, a regimen based on bortezomib (Velcade) was used in combination with rituximab, methotrexate, and intravenous immunoglobulin. Results: The treatment regimen was well tolerated, with no obvious side effects. Patient 1 had a 2,048-fold, and patients 2 and 3 each had a 64-fold, reduction in anti-alglucosidase alfa antibody titer, with concomitant sustained clinical improvement. Conclusion: The addition of bortezomib to immunomodulatory regimens is an effective and safe treatment strategy in infantile Pompe disease, with potentially broader clinical implications.