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METHOD FOR SCREENING FOR SUBSTANCE

Foreign code F130007270
File No. S2011-1164-N0
Posted date Apr 5, 2013
Country WIPO
International application number 2012JP073272
International publication number WO 2013039087
Date of international filing Sep 12, 2012
Date of international publication Mar 21, 2013
Priority data
  • P2011-197931 (Sep 12, 2011) JP
Title METHOD FOR SCREENING FOR SUBSTANCE
Abstract The present invention provides a method for screening for a substance that promotes the induction of induced pluripotent stem cells from cells derived from a body having contracted a disease with which it is not possible to manufacture induced pluripotent stem cells by only the introduction of an initialization gene. The present invention enables the provision of a method for screening for a substance, the method including cultivating, in the presence of a test substance, cells into which an initialization gene has been introduced, the cells being derived from a body having contracted a disease with which it is not possible to manufacture induced pluripotent stem cells by only the introduction of an initialization gene, and segregating out the test substance, which promotes the induction of the cells to induced pluripotent stem cells.
Outline of related art and contending technology BACKGROUND ART
Skeletal dysplasia (Fibrodysplasia ossificans progressiva progressive ossification; FOP) is, progressive, and in a wide range of post-bone to soft tissue and/or intramuscular congenital disorder (non-patent document 1-3). Severe weakness, reduction in life expectancy due to adhesion of the joint, the constraint of the chest with the involvement of ventilation at the major symptoms of the disease in the disorder. The patient FOP, gradually deteriorates the respiratory function, for respiratory failure and ultimately death before the age 40. FOP ectopic bone associated with effective treatment to prevent does not exist. In a recent study, known as BMP1 receptor type ALK2 (ACVR1) activin A receptor by a mutation in 1, this disease has been occurs in the (non-patent document 3-9). And the most common mutation is R206H, the kinase activity of ALK2 is changed, as a result, the constitutive kinase activity of ALK2 is considered to be increased. For example, in the G356D ALK2 mutation as well as a number of schemes such as FOP have been reported and the phenotype of the mutation, they also can affect the kinase activity of ALK2 can cause constitutive activation have been reported (non-patent document 10). ALK2 (G356D) ALK2 (R206H) Of the kinase activity is weaker than the shown, ALK2 clinical change due to a difference in biological activity in variant is suggested (non-patent document 11).
Also, mitochondrial diseases include, diseases caused by mitochondrial functional decline of the general term of, as a representative example of chronic progressive external ocular paralysis syndrome, red rag fibers, myoclonic epilepsy syndrome, fibromyalgia and mitochondrial brain, lactic acidosis, stroke-like symptoms is. Mitochondrial disease refers to, in vivo in all cells at uniform abnormality may occur in the mitochondria from the pathological condition is with or without a variety of translation and, no fundamental therapy is intractable.
In addition, the lysosomes is a disease that is, the lysosomes is one of an intracellular organelle associated with a deficiency caused by disease, resulting in degradation of the original substance to accumulate in the body due to the disease. The lysosomes is a disease that is, loss of the enzyme is different depending on the type of disease and symptoms, there are currently approximately 30 classes of diseases. Is as a treatment method of the lysosomes, enzyme replacement therapy, organ transplantation, bone marrow transplantation and the like are performed, depending on the medical condition is substantially no effect also cannot be obtained, a fundamental therapy is not known.
On the other hand, the cell is derived from the patient's body (iPS cell) is an induced pluripotent stem cell, as well as biomedical research, the effect of agents on cells from a patient as a powerful means for a discussion of expected. IPS cells generated from a particular disease phenotype associated with the disease can be reproduced and are revealed. However, the pathogenicity of the disease specific human iPS cell generation and maintenance of the effect is still unknown how and, progressive fibrosis in bone dysplasia, mitochondrial disease, injuries in the lysosomes disease and the like may be prepared example iPS cells is not known to date.
Scope of claims (In Japanese)請求の範囲 [請求項1]
初期化遺伝子の導入のみでは人工多能性幹細胞を製造できない疾患に罹患した個体に由来する細胞であって初期化遺伝子が導入された細胞を被験物質の存在下で培養し、前記細胞の人工多能性幹細胞への誘導を促進する被験物質を選別することを含む、物質のスクリーニング方法。

[請求項2]
前記疾患がキナーゼの活性の変化に起因する、請求項1に記載の方法。

[請求項3]
前記疾患がアクチビン受容体様キナーゼ2の活性の変化に起因する、請求項1又は2に記載の方法。

[請求項4]
前記疾患が進行性骨化性線維異形成症、ミトコンドリア病又はライソゾーム病である、請求項1から3のいずれか1項に記載の方法。

[請求項5]
前記疾患が進行性骨化性線維異形成症又はライソゾーム病である、請求項1から4のいずれか1項に記載の方法。

[請求項6]
前記疾患が進行性骨化性線維異形成症又はクラッベ病である、請求項1から5のいずれか1項に記載の方法。

[請求項7]
前記細胞がヒトの細胞である、請求項1から6のいずれか1項に記載の方法。

[請求項8]
前記細胞が、配列番号2に示されるアミノ酸配列において第206番目のアルギニンがヒスチジンに変異したアミノ酸配列をコードする遺伝子を有する、請求項7に記載の方法。

[請求項9]
前記細胞が、配列番号2に示されるアミノ酸配列において第356番目のグリシンがアスパラギン酸に変異したアミノ酸配列をコードする遺伝子を有する、請求項7又は8に記載の方法。

[請求項10]
初期化遺伝子が、Oct3/4遺伝子、Klf4遺伝子、Sox2遺伝子、及びc-Myc遺伝子である、請求項1から9のいずれか1項に記載の方法。

[請求項11]
前記細胞が線維芽細胞である、請求項1から10のいずれか1項に記載の方法。

[請求項12]
さらに、アクチビン受容体様キナーゼ2を阻害する被験物質を選別することを含む、請求項1から11のいずれか1項に記載の方法。

[請求項13]
上記疾患に対する治療剤をスクリーニングする方法である、請求項1から12のいずれか1項に記載の方法。

[請求項14]
進行性骨化性線維異形成症、ミトコンドリア病又はライソゾーム病に対する治療剤をスクリーニングする方法である、請求項1から13のいずれか1項に記載の方法。

[請求項15]
進行性骨化性線維異形成症又はライソゾーム病に対する治療剤をスクリーニングする方法である、請求項1から14のいずれか1項に記載の方法。

[請求項16]
進行性骨化性線維異形成症又はクラッベ病に対する治療剤をスクリーニングする方法である、請求項1から15のいずれか1項に記載の方法。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NATIONAL UNIVERSITY CORPORATION KUMAMOTO UNIVERSITY
  • Inventor
  • ERA Takumi
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 IS JP KE KG KM 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 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 ML MR NE SN TD TG
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