AFFITOME® technology in neurodegenerative diseases The doubling advantage

被引:40
作者
Schneeberger, Achim [1 ]
Mandler, Markus [1 ]
Mattner, Frank [1 ]
Schmidt, Walter [1 ]
机构
[1] AFFiRiS AG, Vienna, Austria
来源
HUMAN VACCINES | 2010年 / 6卷 / 11期
关键词
Alzheimer; Parkinson; neurodegenerative diseases; vaccine; immunotherapy; disease modification; A-BETA; ALZHEIMERS-DISEASE; AMYLOID DEPOSITION; IMMUNIZATION; PEPTIDE; PATHOLOGY; NEUROPATHOLOGY; ENCEPHALITIS; PATHOGENESIS; AGGREGATION;
D O I
10.4161/hv.6.11.13217
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Neurodegenerative diseases are still an area of unmet medical need. This is in contrast to our increasing knowledge on their pathology (e. g., Alzheimer's-(AD), Parkinson's (PD) disease). They are driven by the cerebral accumulation and aggregation of specific proteins (e. g., beta-amyloid and hyperphosphorylated tau in the case of AD) in defined brain regions and, as a consequence, death of neurons. Accordingly, removal of given protein aggregates is expected to modify the course of the respective neurodegenerative disease. This has been convincingly demonstrated in animal models of human diseases. However, not every technology that can be used and proves successful in animal models can be translated to the human situation. As highlighted by recent progress in the field of AD research, specific immunotherapy is a viable option in this regard. Given the fact that the aggregates are composed of self-proteins, immunotherapeutic approaches have to consider the issue of potential autoimmunity. This is especially true in case of vaccines. An innovative solution to this problem is offered by the so called AFFITOME (R) technology, which relies on the use of "doubles" of native molecules, functionally mimotopes or AFFITOPES (R) if identified by AFFiRiS, as the antigenic vaccine component.
引用
收藏
页码:948 / 952
页数:5
相关论文
共 27 条
[1]   Neuropathology and pathogenesis of encephalitis following amyloid-β immunization in Alzheimer's disease [J].
Ferrer, I ;
Rovira, MB ;
Guerra, MLS ;
Rey, MJ ;
Costa-Jussá, F .
BRAIN PATHOLOGY, 2004, 14 (01) :11-20
[2]   Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial [J].
Gilman, S ;
Koller, M ;
Black, RS ;
Jenkins, L ;
Griffith, SG ;
Fox, NC ;
Eisner, L ;
Kirby, L ;
Rovira, MB ;
Forette, F ;
Orgogozo, JM .
NEUROLOGY, 2005, 64 (09) :1553-1562
[3]  
GRUNDMAN M, 2008, 10 INT SPR S HONG KO
[4]   β-synuclein regulates Akt activity in neuronal cells -: A possible mechanism for neuroprotection in Parkinson's disease [J].
Hashimoto, M ;
Bar-on, P ;
Ho, G ;
Takenouchi, T ;
Rockenstein, E ;
Crews, L ;
Masliah, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (22) :23622-23629
[5]   β-synuclein inhibits α-synuclein aggregation:: A possible role as an anti-parkinsonian factor [J].
Hashimoto, M ;
Rockenstein, E ;
Mante, M ;
Mallory, M ;
Masliah, E .
NEURON, 2001, 32 (02) :213-223
[6]   Long-term effects of Aβ42 immunisation in Alzheimer's disease:: follow-up of a randomised, placebo-controlled phase I trial [J].
Holmes, Clive ;
Boche, Delphine ;
Wilkinson, David ;
Yadegarfar, Ghasem ;
Hopkins, Vivienne ;
Bayer, Anthony ;
Jones, Roy W. ;
Bullock, Roger ;
Love, Seth ;
Neal, James W. ;
Zotova, Elina ;
Nicoll, James A. R. .
LANCET, 2008, 372 (9634) :216-223
[7]   Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease [J].
Janus, C ;
Pearson, J ;
McLaurin, J ;
Mathews, PM ;
Jiang, Y ;
Schmidt, SD ;
Chishti, MA ;
Horne, P ;
Heslin, D ;
French, J ;
Mount, HTJ ;
Nixon, RA ;
Mercken, M ;
Bergeron, C ;
Fraser, PE ;
St George-Hyslop, P ;
Westaway, D .
NATURE, 2000, 408 (6815) :979-982
[8]   THE CARBOXY TERMINUS OF THE BETA-AMYLOID PROTEIN IS CRITICAL FOR THE SEEDING OF AMYLOID FORMATION - IMPLICATIONS FOR THE PATHOGENESIS OF ALZHEIMERS-DISEASE [J].
JARRETT, JT ;
BERGER, EP ;
LANSBURY, PT .
BIOCHEMISTRY, 1993, 32 (18) :4693-4697
[9]   Nonfibrillar diffuse amyloid deposition due to a γ42-secretase site mutation points to an essential role for N-truncated Aβ42 in Alzheimer's disease [J].
Kumar-Singh, S ;
De Jonghe, C ;
Cruts, M ;
Kleinert, R ;
Wang, R ;
Mercken, M ;
De Strooper, B ;
Vanderstichele, H ;
Löfgren, A ;
Vanderhoeven, I ;
Backhovens, H ;
Vanmechelen, E ;
Kroisel, PM ;
Van Broeckhoven, C .
HUMAN MOLECULAR GENETICS, 2000, 9 (18) :2589-2598
[10]   The ''nonamyloidogenic'' p3 fragment (amyloid beta 17-42) is a major constituent of Down's syndrome cerebellar preamyloid [J].
Lalowski, M ;
Golabek, A ;
Lemere, CA ;
Selkoe, DJ ;
Wisniewski, HM ;
Beavis, RC ;
Frangione, B ;
Wisniewski, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (52) :33623-33631