A PILOT TRIAL OF COP-1 IN EXACERBATING REMITTING MULTIPLE-SCLEROSIS
A PILOT TRIAL OF COP-1 IN EXACERBATING REMITTING MULTIPLE-SCLEROSIS
复制标题
DOI：
10.1056/nejm198708133170703
复制
发表时间：
1987-08-13
影响因子：
158.5
通讯作者：
SELA, M
中科院分区：
文献类型：
--
作者：
BORNSTEIN, MB;MILLER, A;SELA, M
Cop 1是一种模拟髓鞘碱性蛋白的无规聚合物（分子量为14，000至23，000）。由L-丙氨酸、L-谷氨酸、L-赖氨酸和L-酪氨酸聚合而成。它抑制但不诱导实验性过敏性脑脊髓炎，多发性硬化症的动物模型。对动物无毒。在一项双盲、随机、安慰剂对照的初步试验中，我们研究了50名多发性硬化症加重缓解型患者，他们每天自我注射20 mg溶解在1 ml盐水中的Cop 1或单独注射盐水，持续两年。安慰剂组23名患者中有6名（26%）和Cop 1组25名患者中有14名（56%）没有恶化（P = 0.045）。安慰剂组有62例急性加重，Cop 1组有16例，两年平均每例患者分别为2.7和0.6例。在入选时残疾程度较低的患者中（Kurtzke残疾评分，0至2分），安慰剂组有2.7例急性加重，Cop 1组有0.3例。在受影响更大的患者中（Kurtzke残疾评分，3至6），安慰剂组平均有2.7次加重，Cop 1组平均有1.0次加重。两年多来，服用Cop 1的残疾程度较轻的患者平均改善了0.5个Kurtzke单位;服用安慰剂的患者平均恶化了1.2个Kurtzke单位。更多残疾患者恶化0.3（Cop 1组）和0.4（安慰剂组）单位。注射部位刺激和罕见的一过性血管扩张反应被视为副作用。这些结果表明，Cop 1可能对多发性硬化的加重缓解型患者有益，但我们强调，这项研究是初步的，我们的数据需要更广泛的临床试验来证实。
Cop 1 is a random polymer (molecular weight, 14,000 to 23,000) simulating myelin basic protein. It is synthesized by polymerizing L-alanine, L-glutamic acid, L-lysine , and L-tyrosine. It suppresses but does not induce experimental allergic encephalomyelitis, an animal model of multiple sclerosis. It is not toxic in animals. In a double-blind, randomized, placebo-controlled pilot trial, we studied 50 patients with the exacerbating-remitting form of multiple sclerosis, who self-injected either 20 mg of Cop 1 dissolved in 1 ml of saline or saline alone daily for two years. Six of 23 patients in the placebo group (26 percent) and 14 of 25 patients in the Cop 1 group (56 percent) had no exacerbations (P = 0.045). There were 62 exacerbations in the placebo group and 16 in the Cop 1 group, yielding two-year averages of 2.7 and 0.6 per patient, respectively. Among patients who were less disabled on entry (Kurtzke disability score, 0 to 2), there were 2.7 exacerbations in the placebo group and 0.3 in the Cop 1 group over two years. Among patients who were more affected (Kurtzke disability score, 3 to 6), there was an average of 2.7 exacerbations in the placebo group and 1.0 in the Cop 1 group. Over two years, less disabled patients taking Cop 1 improved an average of 0.5 Kurtzke units; those taking placebo worsened an average of 1.2 Kurtzke units. More disabled patients worsened by 0.3 (Cop 1 group) and 0.4 (placebo group) unit. Irritation at injection sites and rare, transient vasomotor responses were observed as side effects. These results suggest that Cop 1 may be beneficial in patients with the exacerbating-remitting form of multiple sclerosis, but we emphasize that the study is a preliminary one and our data require confirmation by a more extensive clinical trial.