| <DIV>多伦多(EGMN)——一项小规模II期试验表明，静脉内免疫球蛋白治疗可减轻轻中度阿尔茨海默病患者的脑萎缩。试验结果提示，这种血液制品中的特定IgG抗体成分可能成为该病的候选治疗药物。</DIV>
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<DIV>4月14日，在美国神经病学会2010年年会上，Norman Relkin博士在一篇壁报论文中称：“相对于阿尔茨海默病的现有治疗手段，这种治疗的前景非常乐观，它能使脑萎缩率下降到同龄人正常水平。”</DIV>
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<DIV>在阿尔茨海默病(AD)患者中，现已知脑萎缩会导致侧脑室扩大。脑室容量增大则可导致认知能力下降以及AD神经系统病变加重。</DIV>
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<DIV>Relkin博士及其同事在24例轻中度AD患者中开展了一项为期6个月、双盲、随机试验，将静脉内免疫球蛋白(IVIG)治疗与安慰剂进行了对照。在该试验的12个月扩展期内，16例最初被随机分配至接受IVIG的患者继续接受相同剂量的IVIG，而另外8例安慰剂组患者则经二次随机分组后，分别接受4种IVIG剂量之一。研究者在试验中采用的是百特公司生产的IVIG产品，产品名称是Gammagard。</DIV>
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<DIV>IVIG减轻脑萎缩的作用呈剂量依赖性，剂量越大，萎缩程度越轻。在接受IVIG治疗的患者中，有14例在基线时接受了MRI容量分析，18个月后再次进行MRI容量分析，结果显示，侧脑室容量的年增幅在0.4 mg/kg，每2周1次剂量组中最低 (2.4%)，在0.2 mg/kg，每2周1次剂量组中最高 (11.2%)。试验中，IVIG的给药剂量为0.2 mg/kg(每2周1次) ~ 0.8 mg/kg(每4周1次)。</DIV>
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<DIV>在IVIG治疗期间(所有剂量合并分析)，侧脑室的容量每年平均增加6.7%，而6例接受安慰剂治疗的患者每年增加12.3%，差异有统计学意义。</DIV>
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<DIV>只有0.4 mg/kg(每2周1次)剂量组患者的大脑总容量的变化显著小于安慰剂组患者(分别为-0.62%对 -2.24%)。</DIV>
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<DIV>美国纽约长老会医院/ Weill Cornell医学中心记忆障碍研究项目主任Relkin博士说：“除了大脑影像学检查外，我们之前还发现治疗后患者的脑脊液和血浆淀粉样蛋白水平都发生了变化……脑代谢水平也有变化。”</DIV>
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<DIV>脑萎缩减轻与18个月时临床转归的改善显著相关，临床转归的评价工具包括临床总体改变印象量表以及阿尔茨海默病评价量表中的认知分量表。患者的基线特征与MRI容量分析结果无关。</DIV>
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<DIV>Relkin博士在采访中说：“这项试验探讨了很多方面的问题，因此下一步应该确定的是IVIG中的什么成分产生了这种治疗效应……我们已知IVIG能够非常好地补充抗淀粉样蛋白抗体。这是我们主要考虑的成分，但我们目前尚不确定是否就是这种成分在发挥治疗效应。”</DIV>
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<DIV>目前，Relkin博士及其同事正在360例轻中度AD患者中开展另一项IVIG多中心III期试验。除此之外，他们还在基于细胞培养的研究以及临床前动物模型中对IVIG中的抗体亚型进行检测，以确定哪些成分具有治疗相关性。</DIV>
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<DIV>Relkin博士说：“我们并不鼓励人们标签外使用IVIG治疗阿尔茨海默病，即便这些小规模试验表明IVIG的安全性和耐受性都很好。在此之前，从未有人在阿尔茨海默病患者人群中对IVIG进行过研究。”</DIV>
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<DIV>百特公司是IVIG I 期和II期试验的申办方，同时也得到了花旗集团基金会和美国国立卫生研究院(NIH)的支持。III期试验则由百特公司和NIH联合主办。Relkin博士声明除了接受百特公司提供的IVIG试验研究经费外，无其他相关利益冲突。</DIV>
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<DIV class=NewsInfo><SPAN>TORONTO (EGMN) – Intravenous immunoglobulin therapy reduced brain atrophy in patients with mild to moderate Alzheimer’s disease in a small phase II trial. The finding suggests that specific IgG antibody components found in the blood product might be treatment candidates for the disease.</DIV>
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<P>“Relative to what we have available right now [to treat Alzheimer’s disease], this is a very promising outcome, and it’s associated with a reduction in the rate of brain atrophy comparable to age-matched normals,” Dr. Norman Relkin said April 14 during a poster presentation at the annual meeting of the American Academy of Neurology.</P>
<P>Enlargement of the cerebral lateral ventricles is known to occur as a consequence of brain atrophy in Alzheimer’s disease (AD). This increase in ventricular volume is correlated with cognitive decline and increases in Alzheimer’s disease neuropathology.</P>
<P>Dr. Relkin and his colleagues compared intravenous immunoglobulin (IVIG) therapy against placebo in a 6-month, double-blind, randomized study of 24 patients with mild to moderate AD. In a 12-month extension phase of the study, 16 patients who originally were randomized to IVIG continued to receive the same doses of IVIG, whereas 8 placebo-treated patients were rerandomized to one of four doses of IVIG. The investigators used an IVIG product produced by Baxter Healthcare called Gammagard.</P>
<P>IVIG exhibited a dose-dependent effect on brain atrophy in which higher doses resulted in less atrophy. Among 14 IVIG-treated patients who underwent volumetric MRI at baseline, after 18 months, the yearly increase in lateral ventricle volume measured with volumetric MRI was lowest in patients treated with 0.4 mg/kg every 2 weeks (2.4%) and highest in those treated with 0.2 mg/kg every 2 weeks (11.2%). The doses of IVIG given to patients ranged from 0.2 mg/kg every 2 weeks to 0.8 mg/kg every 4 weeks.</P>
<P>The volume of the lateral ventricles increased by a mean of 6.7% per year during treatment with IVIG (all doses combined), which was significantly lower than the 12.3% annual rate of increase observed in six placebo-treated patients.</P>
<P>Only the 0.4-mg/kg dose of IVIG given every 2 weeks resulted in significantly less change in total brain volume than did treatment with placebo (–0.62% vs. –2.24%, respectively).</P>
<P>“In addition to the brain imaging, we have previously shown changes in cerebrospinal fluid and plasma amyloid levels ... and levels of cerebral metabolism changing in response to treatment,” said Dr. Relkin, director of the Memory Disorders Program at New York–Presbyterian Hospital/Weill Cornell Medical Center.</P>
<P>The reduction in brain atrophy was significantly correlated with improvement in clinical outcomes at 18 months on the Clinical Global Impression of Change and the cognitive subscale of the Alzheimer’s Disease Assessment Scale. Baseline characteristics of the patients were not correlated with volumetric MRI outcomes.</P>
<P>“This is a ‘kitchen sink’ approach, so the next step is to find what is in [IVIG] that is causing the therapeutic effect. ... We know that it has a fairly good complement of antiamyloid antibodies. Those are prime candidates, but we don’t know for sure yet that those are ones responsible for a therapeutic effect,” Dr. Relkin said in an interview.</P>
<P>In addition to an ongoing, multicenter, phase III study of IVIG in 360 patients with mild to moderate AD, Dr. Relkin and his colleagues are testing subsets of antibodies within IVIG in cell culture–based studies and preclinical animal models to see which components are therapeutically relevant.</P>
<P>“We are not encouraging people to use [IVIG] off-label for Alzheimer’s disease, even though it has been safe and well tolerated in these small studies,” Dr. Relkin said. “It has never been studied in the Alzheimer’s population before.”</P>
<P>Baxter Healthcare sponsored the phase I and II studies of IVIG, with additional support from the Citigroup Foundation and the U.S. National Institutes of Health. The phase III trial is cosponsored by Baxter and the NIH. Dr. Relkin reported no relevant disclosures besides receiving a research grant from Baxter Healthcare to study IVIG.</P></SPAN></SPAN></DIV></DIV></DIV> |
