Top > Search of International Patents > TREATMENT AGENT FOR COGNITIVE DISORDERS, INDUCED BY AMYLOID β-PROTEIN, THERAPEUTIC AGENT FOR ALZHEIMER'S DISEASE, AND TREATMENT METHOD AND PATHOLOGICAL ANALYSIS METHOD RELATED TO THESE

TREATMENT AGENT FOR COGNITIVE DISORDERS, INDUCED BY AMYLOID β-PROTEIN, THERAPEUTIC AGENT FOR ALZHEIMER'S DISEASE, AND TREATMENT METHOD AND PATHOLOGICAL ANALYSIS METHOD RELATED TO THESE

Foreign code F150008246
Posted date Mar 27, 2015
Country WIPO
International application number 2014JP060665
International publication number WO 2014171434
Date of international filing Apr 15, 2014
Date of international publication Oct 23, 2014
Priority data
  • P2013-088319 (Apr 19, 2013) JP
Title TREATMENT AGENT FOR COGNITIVE DISORDERS, INDUCED BY AMYLOID β-PROTEIN, THERAPEUTIC AGENT FOR ALZHEIMER'S DISEASE, AND TREATMENT METHOD AND PATHOLOGICAL ANALYSIS METHOD RELATED TO THESE
Abstract The present invention addresses the issue of providing an anti-Alzheimer's agent that uses an amyloid β-protein as the mechanism of action therefor but that is different from conventional mechanisms of action. This therapeutic agent for Alzheimer's disease contains a cognitive disorder treatment agent induced by an amyloid β-protein containing a peptide comprising an amino acid sequence indicated by SEQ ID NO. 1, or a peptide similar to same, in particular a peptide including an amino acid sequence indicated by SEQ ID NO. 2 being a partial sequence of SEQ ID NO. 1; and is characterized by containing said treatment agent. SEQ ID NO. 1: VLSSQQFLHRGHQPPPEMAGHSLASSHRNSMIPSAAT; SEQ ID NO. 2: HRGHQPPPEMA
Outline of related art and contending technology BACKGROUND ART
Alzheimer's disease, cognitive decline (or remembering) the main condition that neurological disease. In particular in elderly is even though the predilection, there is no effective therapeutic, are worn out in aging society and the serious problem in developed countries. In the postmortem brain of Alzheimer's disease patients which neuritic plaques observed, this is' amyloid β protein ' aggregates with are known. Then, the amyloid β protein is the main cause of Alzheimer's disease is, by numerous studies in the widely accepted.
Amyloid β protein, a precursor thereof 'the amyloid precursor protein' generated from. The amyloid precursor protein and, on neural cell membranes is a membrane protein. In the normal brain, its extracellular domain α secretase, γ-secretase in the cell membrane and then are cut in the domain, the peptide is referred to as p3 outside of the cell production, is released. This is' non-amyloid generation path ' known as, amyloid β protein is not generated (non-patent document 1). In the normal brain, but the extracellular domain of the β-secretase is several % to truncated, extracellular amyloid β protein are secreted. However, in the brain Alzheimer's disease, amyloid β production amount of the protein will be increased, the aggregation of amyloid β protein species of high so as to produce are considered. Amyloid β protein with this property, finally Alzheimer's disease patients of senile plaques formed (amyloid aggregates), deposition is observed in the brain.
Amyloid β protein is found to have a cut, gradually aggregated, finally senile plaques (amyloid aggregates) are formed, agglomeration processes' oligomeric forms (amyloid β protein that associated with the several) ' in, known to be strong neurotoxicity. Amyloid β protein is in oligomeric forms, memory, learning of the neural phenomenon essential to inhibit synaptic plasticity, in vitro, both in vivo have been reported (non-patent document 2, 3). In addition, this oligomer administered to the body in the mouse brain, storage, can be lost to the learning ability have been reported (non-patent document 4, 5). A recent study, and the oligomeric forms of long-term exposure, and the like can also occur in neuronal cell death has been reported (non-patent document 6), to cause the onset of Alzheimer's disease has been paid attention as a substance.
In this way, as the cause of the amyloid β protein Alzheimer's disease is widely recognized that regardless of the fact that, currently clinically used in the therapeutic agent is Alzheimer's disease, amyloid β protein in such a manner that this design is not. Specifically, used as a therapeutic agent Alzheimer's disease (Patent Document 1) memantine or donepezil (Patent Document 2) is, and the acetylcholinesterase inhibitor respectively act as NMDA receptor inhibitors, amyloid β protein does not interact with. Since the agent is a so-called address, a dramatic improvement in the effect for Alzheimer's disease is at present.
In response to such a background, based on the mechanism of action (amyloid protein) new Alzheimer's development of therapeutics has been promoted. 1 Is one, the amyloid precursor protein from the production of amyloid β protein and attempted to attempt, the development of secretase control agent (non-patent document 1). Among them, development of γ secretase inhibitors and the most advanced, Begacestat Semagacestat (Patent Document 3) or the like (Patent Document 4), efforts have been performed and the clinical development. Another has attracted attention as a therapy is, amyloid β protein in the brain is removed and antibody-recognized, antibody therapy. Actually, solanezumab Bapineuzumab (Patent Document 5) or the like, this method has been developed for clinical history is.
However, with the center of the present development of amyloid protein Alzheimer's mechanism of action and there are problems that the therapeutic agent may be known. With respect to the γ secretase inhibitors, γ secretase substrates in the first place as well as the amyloid precursor protein, are known to be near about 100 (non-patent document 7). And includes an, important cell differentiation which may include Notch receptor (non-patent document 8), concern about side effects. Actually, was a strong candidate for the γ secretase inhibitors as Semagacestat is, developed in the year 2010 the third phase clinical trials are terminated. Anti-amyloid β antibody for the antibody therapy, vasculitis and vascular cerebral edema and the like which can occur, in fact, is promising as a therapeutic agent was also Bapineuzumab antibody, was developed in 2012 is stopped.
In addition, the stroma of the γ secretase is, cut the extracellular domain of the amyloid peptide may be ejected in some known (non-patent document 9, 10). These peptides are indicative of the activity since the γ secretase, fragment was cut to a biomarker of the invention of the Alzheimer's disease are some (Patent Document 6, 7). Also, referred to as Alcadein-β is membrane protein in vivo, cleaved by γ-secretase, by may be cut by further α secretase, 37 amino acid peptide (VLSSQQFLHRGHQPPPEMAGHSLASSHRNSMIPSAAT) also known being produced in the (non-patent document 11).
However, such a peptide to Alzheimer's disease is the idea of control agent, the present finding, is assumed for the state of the art is difficult, and thus in no way has been reported.
Scope of claims (In Japanese)請求の範囲 [請求項1]
 下記(I)~(VI)のいずれかに該当するペプチドを有効成分として含有することを特徴とする、アミロイドβ蛋白質により誘発される認知障害の治療剤。
 (I)配列番号1で表されるアミノ酸配列からなるペプチド。
VLSSQQFLHRGHQPPPEMAGHSLASSHRNSM
IPSAAT                  (配列番号1)
 (II)配列番号1で表されるアミノ酸配列に対して1~3個のアミノ酸が、欠失、付加、置換または側鎖の修飾のいずれか一種以上により改変されたアミノ酸配列からなるペプチド。
 (III)配列番号2で表されるアミノ酸配列を含む、配列番号1で表されるアミノ酸配列の部分配列からなるペプチド。
HRGHQPPPEMA             (配列番号2)
 (IV)配列番号2で表されるアミノ酸配列を含む、配列番号1で表されるアミノ酸配列の部分配列に対して、1~2個のアミノ酸が、欠失、付加、置換または側鎖の修飾のいずれか一種以上により改変されたアミノ酸配列からなるペプチド。
 (V)配列番号2で表されるアミノ酸配列を含み、当該アミノ酸配列のN末端および/またはC末端に合計で1~50個のアミノ酸が付加されたアミノ酸配列(ただし、配列番号1で表されるアミノ酸配列の全部または一部と一致する場合を除く。)からなるペプチド。
 (VI)配列番号2で表されるアミノ酸配列に対して、1~2個のアミノ酸が、欠失、付加(N末端および/またはC末端に対する付加を除く。)、置換または側鎖の修飾のいずれか一種以上により改変されたアミノ酸配列を含み、当該改変されたアミノ酸配列のN末端および/またはC末端に合計で1~50個のアミノ酸が付加されたアミノ酸配列からなるペプチド。

[請求項2]
 請求項1に記載の治療剤を含有する、アルツハイマー病治療薬。

[請求項3]
 請求項1に記載の治療剤を、アミロイドβ蛋白質により誘発される認知障害を発症した哺乳類(ヒトを除く)またはそのモデル動物に投与するステップを含むことを特徴とする、アミロイドβ蛋白質により誘発される認知障害の治療方法。

[請求項4]
 請求項2に記載の治療薬を、アルツハイマー病に罹患した哺乳類(ヒトを除く)またはそのモデル動物に投与するステップを含むことを特徴とする、アルツハイマー病の治療方法。

[請求項5]
 前記(I)~(VI)のいずれかに該当するペプチドを、アミロイドβ蛋白質により誘発される認知障害を発症した哺乳類(ヒトを除く)またはそのモデル動物に投与するステップ、あるいはそのモデル細胞としての培養神経細胞または神経細胞に発現している生体分子に添加するステップを含むことを特徴とする、アミロイドβ蛋白質により誘発される認知障害の病態解析方法。

[請求項6]
 前記(I)~(VI)のいずれかに該当するペプチドを、アルツハイマー病に罹患した哺乳類(ヒトを除く)またはそのモデル動物に投与するステップ、あるいはそのモデル細胞としての培養神経細胞または神経細胞に発現している生体分子に添加するステップを含むことを特徴とする、アルツハイマー病の病態解析方法。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY
  • HOKKAIDO UNIV
  • Inventor
  • INOUE, Tsuyoshi
  • SUZUKI, Toshiharu
  • BAN, Saori
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN TD TG

PAGE TOP

close
close
close
close
close
close