Saint Louis大学科学家最近发现，一种特殊的蛋白能通过注射到老鼠体内来逆转患有动物阿兹海默症的老鼠的认知问题。
这种蛋白是免疫球蛋白M（IgM）的一部分，它能结合到大脑中淀粉样β蛋白上，并防止其转变为造成阿兹海默症的毒性物质。
Saint Louis大学老年病学、药理学和生理学教授William A. Banks表示：“我们针对动物模型的研究显示抗体能被用于治疗阿兹海默症。这是人们致力于做的事情－在大脑中置入合适剂量的抗体，然后治疗疾病，而这种抗体能实现以上效果。”
Banks表示研究结果令人惊讶，因为IgM比抗体IgG大五倍，而后者是治疗阿兹海默症的潜在手段之一。由于其体积较大，科学家并不认为它能穿过血脑屏障，血脑屏障是防止外来物质进入大脑的一层保护性膜。
Banks说：“我们和耶路撒冷希伯来大学的Michael Steinitz合作，他发明了一种属于IgM的抗体，并且能更好的结合到淀粉样β蛋白上。”Banks同时也是St. Louis的老兵医疗中心内科医师。
Banks说：“该化合物相比IgG能更好的进入大脑中。”静脉中注入单剂量的IgM能有效逆转年老老鼠的认知损伤，这些老鼠发生了一种基因变异，这和造成阿兹海默症病人的缺陷类似。以上研究结果发表在了8月份的Experimental Neurology上。 （教育部科技发展中心）
原文链接：http://www.physorg.com/news111062928.html
原始出处:
Experimental Neurology
Volume 206, Issue 2, August 2007, Pages 248-256
Anti-amyloid beta protein antibody passage across the blood–brain barrier in the SAMP8 mouse model of Alzheimer's disease: An age-related selective uptake with reversal of learning impairment
William A. Banksa, b, , , Susan A. Farra, b, John E. Morleya, b, Kathy M. Wolfa, b, Valeria Geylisc and Michael Steinitzc
aGeriatrics Research Educational and Clinical Center, Veterans Affairs Medical Center-St. Louis, USA
bSaint Louis University School of Medicine, Division of Geriatrics, Department of Internal Medicine, USA
cDepartment of Pathology, The Hebrew University-Hadassah Medical School, POB 12272, Jerusalem 91120, Israel
Received 28 March 2007; revised 2 May 2007; accepted 3 May 2007. Available online 22 May 2007.
Abstract
Amyloid beta protein (Aβ) levels are elevated in the brain of Alzheimer's disease patients. Anti-Aβ antibodies can reverse the histologic and cognitive impairments in mice which overexpress Aβ. Passive immunization appears safer than vaccination and treatment of patients will likely require human rather than xenogenic antibodies. Effective treatment will likely require antibody to cross the blood–brain barrier (BBB). Unfortunately, antibodies typically cross the BBB very poorly and accumulate less well in brain than even albumin, a substance nearly totally excluded from the brain. We compared the ability of two anti-Aβ human monoclonal IgM antibodies, L11.3 and HyL5, to cross the BBB of young CD-1 mice to that of young and aged SAMP8 mice. The SAMP8 mouse has a spontaneous mutation that induces an age-related, Aβ-dependent cognitive deficit. There was preferential uptake of intravenously administered L11.3 in comparison to HyL5, albumin, and a control human monoclonal IgM (RF), especially by hippocampus and olfactory bulb in aged SAMP8 mice. Injection of L11.3 into the brains of aged SAMP8 mice reversed both learning and memory impairments in aged SAMP8 mice, whereas IgG and IgM controls were ineffective. Pharmacokinetic analysis predicted that an intravenous dose 1000 times higher than the brain injection dose would reverse cognitive impairments. This predicted intravenous dose reversed the impairment in learning, but not memory, in aged SAMP8 mice. In conclusion, an IgM antibody was produced that crosses the BBB to reverse cognitive impairment in a murine model of Alzheimer's disease.
Keywords: Alzheimer's disease; Amyloid beta protein; Therapeutics; Monoclonal antibody; Blood–brain barrier; IgM; Passive immunization; Cognition
