Immunotherapy for Alzheimer's disease.
Immunotherapy for Alzheimer's disease.
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DOI：
10.1111/j.1365-2796.2010.02315.x
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发表时间：
2011-01
影响因子：
11.1
通讯作者：
Morgan D
中科院分区：
文献类型：
--
作者：
Morgan D
1999年，一种疫苗方法被发现可以减少过度产生淀粉样前体蛋白的转基因小鼠的淀粉样沉积。紧接着，疫苗或被动免疫疗法可以挽救这些小鼠的记忆缺陷。最初的人体临床试验显示，在一部分患者中有明显的自身免疫反应，但也有一些认知益处和淀粉样蛋白清除的病例。在小鼠模型中进行被动免疫治疗的进一步研究证实了抗淀粉样蛋白抗体的特殊清除能力，即使在老年小鼠中也是如此。然而，与实质淀粉样蛋白清除平行的是微血管化的出现和血管淀粉样蛋白沉积的增加。被动免疫治疗的其他临床试验证实，在一些患者中偶尔出现微出血和血管源性水肿，特别是载脂蛋白E4基因型患者。正电子发射断层扫描的最新数据表明，被动免疫抗A β抗体的试验参与者在治疗18个月后与淀粉样蛋白结合配体的信号减少。几种抗A β免疫疗法已经达到3期测试，免疫疗法可能是阿尔茨海默病淀粉样蛋白假说的第一个测试。鉴定保留淀粉样蛋白清除且不良反应较少的抗体变体仍然是该领域转化研究的主要焦点。
In 1999 a vaccine approach was found to reduce amyloid deposits in transgenic mice overproducing the amyloid precursor protein. This was followed closely by demonstrations that vaccines or passive immunotherapy could rescue memory deficits in these mice. Initial human clinical trials revealed apparent autoimmune reactions in a subset of patients, but also some cases of cognitive benefit and amyloid clearance. Further work with passive immunotherapy in mouse models confirmed exceptional clearing abilities of anti-amyloid antibodies even in older mice. However, in parallel with parenchymal amyloid clearance was the appearance of microhemorrhages and increased vascular amyloid deposition. Additional clinical trials with passive immunotherapy confirmed occasional appearance of microhemorrhage and occurrence of vasogenic edema in some patients, particularly those with the apolipoprotein E4 genotype. Recent data with positron emission tomography demonstrates trial participants passively immunized with anti-Aβ antibodies have reduced signals with amyloid binding ligands after 18 mo of therapy. Several anti-Aβ immunotherapies have reached phase 3 testing and immunotherapy is likely to be the first test of the amyloid hypothesis of Alzheimer’s disease. Identifying antibody variants that retain amyloid clearance with fewer adverse reactions remains a major focus of translational research in this area.
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DOI：
10.1523/jneurosci.4560-08.2009
发表时间：
2009-04-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Karlnoski RA;Rosenthal A;Kobayashi D;Pons J;Alamed J;Mercer M;Li Q;Gordon MN;Gottschall PE;Morgan D
通讯作者：
Morgan D
DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
6.2
作者：
Karlnoski, Rachel A.;Rosenthal, Arnon;Alamed, Jennifer;Ronan, Victoria;Gordon, Marcia N.;Gottschall, Paul E.;Grimm, Jan;Pons, Jaume;Morgan, Dave
通讯作者：
Morgan, Dave
影响因子：
82.9
作者：
Holcomb, L;Gordon, MN;Duff, K
通讯作者：
Duff, K
影响因子：
82.9
作者：
Deane, R;Yan, SD;Zlokovic, B
通讯作者：
Zlokovic, B