Department of Neurology, University Hospital Basel, Petersgraben, Basel, Switzerland.
J Neurol. 2012 Jul;259(7):1375-82. doi: 10.1007/s00415-011-6361-x. Epub 2012 Jan 6.
Persistent black holes (PBH) are associated with axonal loss and disability progression in multiple sclerosis (MS). The objective of this work was to determine if BHT-3009, a DNA plasmid-encoding myelin basic protein (MBP), reduces the risk of new lesions becoming PBH, compared to placebo, and to test if pre-treatment serum anti-MBP antibody levels impact on the effect of BHT-3009 treatment. In this retrospective, blinded MRI study, we reviewed MRI scans of 155 MS patients from a double-blind, randomized, phase II trial with three treatment arms (placebo, 0.5 and 1.5 mg BHT-3009). New lesions at weeks 8 and 16 were tracked at week 48 and those appearing as T1-hypointense were classified as PBH. A subset of 46 patients with available pre-treatment serum anti-MBP IgM levels were analyzed separately. Overall, there was no impact of treatment on the risk for PBH. However, there was a significant interaction between anti-MBP antibodies and treatment effect: patients receiving 0.5 mg BHT-3009 showed a reduced risk of PBH with higher antibody levels compared to placebo (p < 0.01). Although we found no overall reduction of the risk for PBH in treated patients, there may be an effect of low-dose BHT-3009, depending on the patients' pre-treatment immune responses.
持续性黑洞（PBH）与多发性硬化症（MS）中的轴突损失和残疾进展有关。这项工作的目的是确定与安慰剂相比，编码髓鞘碱性蛋白（MBP）的 DNA 质粒 BHT-3009 是否降低了新病变发展为 PBH 的风险，并测试治疗前血清抗 MBP 抗体水平是否影响 BHT-3009 治疗的效果。在这项回顾性、盲法 MRI 研究中，我们回顾了来自一项双盲、随机、二期试验的 155 名 MS 患者的 MRI 扫描，该试验有三个治疗组（安慰剂、0.5 和 1.5mg BHT-3009）。在第 48 周追踪第 8 周和第 16 周出现的新病变，表现为 T1 低信号的病变被归类为 PBH。对 46 名有治疗前血清抗 MBP IgM 水平的患者进行了单独分析。总体而言，治疗对 PBH 的风险没有影响。然而，抗 MBP 抗体与治疗效果之间存在显著的相互作用：与安慰剂相比，接受 0.5mg BHT-3009 治疗的患者在抗体水平较高时 PBH 的风险降低（p<0.01）。尽管我们在接受治疗的患者中没有发现 PBH 风险总体降低，但低剂量 BHT-3009 可能会根据患者的治疗前免疫反应产生影响。
