Saint Louis大學(xué)科學(xué)家最近發(fā)現(xiàn)，一種特殊的蛋白能通過注射到老鼠體內(nèi)來逆轉(zhuǎn)患有動物阿茲海默癥的老鼠的認(rèn)知問題。
這種蛋白是免疫球蛋白M（IgM）的一部分,，它能結(jié)合到大腦中淀粉樣β蛋白上，并防止其轉(zhuǎn)變?yōu)樵斐砂⑵澓ＤY的毒性物質(zhì),。
Saint Louis大學(xué)老年病學(xué),、藥理學(xué)和生理學(xué)教授William A. Banks表示：“我們針對動物模型的研究顯示抗體能被用于治療阿茲海默癥。這是人們致力于做的事情－在大腦中置入合適劑量的抗體,，然后治療疾病,，而這種抗體能實(shí)現(xiàn)以上效果。”
Banks表示研究結(jié)果令人驚訝,，因?yàn)镮gM比抗體IgG大五倍,，而后者是治療阿茲海默癥的潛在手段之一。由于其體積較大,，科學(xué)家并不認(rèn)為它能穿過血腦屏障,，血腦屏障是防止外來物質(zhì)進(jìn)入大腦的一層保護(hù)性膜。
Banks說：“我們和耶路撒冷希伯來大學(xué)的Michael Steinitz合作,，他發(fā)明了一種屬于IgM的抗體,，并且能更好的結(jié)合到淀粉樣β蛋白上。”Banks同時也是St. Louis的老兵醫(yī)療中心內(nèi)科醫(yī)師,。
Banks說：“該化合物相比IgG能更好的進(jìn)入大腦中,。”靜脈中注入單劑量的IgM能有效逆轉(zhuǎn)年老老鼠的認(rèn)知損傷，這些老鼠發(fā)生了一種基因變異,，這和造成阿茲海默癥病人的缺陷類似,。以上研究結(jié)果發(fā)表在了8月份的Experimental Neurology上。 （教育部科技發(fā)展中心）
原文鏈接：http://www.physorg.com/news111062928.html
原始出處:
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
