Fusion antibody for Alzheimer's disease with bidirectional transport across the blood-brain barrier and Aβ fibril disaggregation

被引：105

作者：

Boado, Ruben J.

Zhang, Yufeng

Zhang, Yun

Xia, Chun-Fang

Pardridge, William M.

机构：

[1] Calif State Univ Los Angeles, Dept Med, Los Angeles, CA 90024 USA

[2] ArmaGen Technol Inc, Santa Monica, CA USA

来源：

BIOCONJUGATE CHEMISTRY | 2007年 / 18卷 / 02期

关键词：

D O I：

10.1021/bc060349x

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Delivery of monoclonal antibody therapeutics across the blood-brain barrier is an obstacle to the diagnosis or therapy of CNS disease with antibody drugs. The immune therapy of Alzheimer's disease attempts to disaggregate the amyloid plaque of Alzheimer's disease with an anti-A beta monoclonal antibody. The present work is based on a three-step model of immune therapy of Alzheimer's disease: (1) influx of the anti-A beta monoclonal antibody across the blood-brain barrier in the blood to brain direction, (2) binding and disaggregation of A beta fibrils in brain, and (3) efflux of the anti-A beta monoclonal antibody across the blood-brain barrier in the brain to blood direction. This is accomplished with the genetic engineering of a trifunctional fusion antibody that binds (1) the human insulin receptor, which mediates the influx from blood to brain across the blood-brain barrier, (2) the A beta fibril to disaggregate amyloid plaque, and (3) the Fc receptor, which mediates the efflux from brain to blood across the blood-brain barrier. This fusion protein is a new antibody-based therapeutic for Alzheimer's disease that is specifically engineered to cross the human blood-brain barrier in both directions.

引用

收藏

页码：447 / 455

页数：9

相关论文

共 34 条

[21] CATIONIZATION OF A MONOCLONAL-ANTIBODY TO THE HUMAN-IMMUNODEFICIENCY-VIRUS REV PROTEIN ENHANCES CELLULAR UPTAKE BUT DOES NOT IMPAIR ANTIGEN-BINDING OF THE ANTIBODY [J].

PARDRIDGE, WM ;

BICKEL, U ;

BUCIAK, J ;

YANG, J ;

DIAGNE, A ;

AEPINUS, C .

IMMUNOLOGY LETTERS, 1994, 42 (03) :191-195

[22] Peripheral injections of Freund's adjuvant in mice provoke leakage of serum proteins through the blood-brain barrier without inducing reactive gliosis [J].

Rabchevsky, AG ;

Degos, JD ;

Dreyfus, PA .

BRAIN RESEARCH, 1999, 832 (1-2) :84-96

[23] STRUCTURAL-CHANGES IN THE RAT-BRAIN AFTER CAROTID INFUSIONS OF HYPEROSMOLAR SOLUTIONS - AN ELECTRON-MICROSCOPIC STUDY [J].

SALAHUDDIN, TS ;

JOHANSSON, BB ;

KALIMO, H ;

OLSSON, Y .

ACTA NEUROPATHOLOGICA, 1988, 77 (01) :5-13

[24] Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease:: Relationships to β-amyloid deposition and neurotransmitter abnormalities [J].

Savonenko, A ;

Xu, GM ;

Melnikova, T ;

Morton, JL ;

Gonzales, V ;

Wong, MPF ;

Price, DL ;

Tang, F ;

Markowska, AL ;

Borchelt, DR .

NEUROBIOLOGY OF DISEASE, 2005, 18 (03) :602-617

[25] Immunization with amyloid-β attenuates Alzheimer disease-like pathology in the PDAPP mouse [J].

Schenk, D ;

Barbour, R ;

Dunn, W ;

Gordon, G ;

Grajeda, H ;

Guido, T ;

Hu, K ;

Huang, JP ;

Johnson-Wood, K ;

Khan, K ;

Kholodenko, D ;

Lee, M ;

Liao, ZM ;

Lieberburg, I ;

Motter, R ;

Mutter, L ;

Soriano, F ;

Shopp, G ;

Vasquez, N ;

Vandevert, C ;

Walker, S ;

Wogulis, M ;

Yednock, T ;

Games, D ;

Seubert, P .

NATURE, 1999, 400 (6740) :173-177

[26] Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier [J].

Schlachetzki, F ;

Zhu, CN ;

Pardridge, WM .

JOURNAL OF NEUROCHEMISTRY, 2002, 81 (01) :203-206

[27] THE INTRACELLULAR COMPONENT OF CELLULAR 3-(4,5-DIMETHYLTHIAZOL-2-YL)-2,5-DIPHENYLTETRAZOLIUM BROMIDE (MTT) REDUCTION IS SPECIFICALLY INHIBITED BY BETA-AMYLOID PEPTIDES [J].

SHEARMAN, MS ;

HAWTIN, SR ;

TAILOR, VJ .

JOURNAL OF NEUROCHEMISTRY, 1995, 65 (01) :218-227

[28] Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human FcγRIII and antibody-dependent cellular toxicity [J].

Shields, RL ;

Lai, J ;

Keck, R ;

O'Connell, LY ;

Hong, K ;

Meng, YG ;

Weikert, SHA ;

Presta, LG .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (30) :26733-26740

[29] Monoclonal antibodies inhibit in vitro fibrillar aggregation of the Alzheimer beta-amyloid peptide [J].

Solomon, B ;

Koppel, R ;

Hanan, E ;

Katzav, T .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (01) :452-455

[30] Disaggregation of Alzheimer beta-amyloid by site-directed mAb [J].

Solomon, B ;

Koppel, R ;

Frankel, D ;

HananAharon, E .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :4109-4112

← 1 2 3 4 →