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1. (WO2014178555) PHARMACEUTICAL COMPOSITION FOR ALLEVIATING OR TREATING AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE COMPRISING DNA METHYLATION INHIBITOR
Latest bibliographic data on file with the International Bureau   

Pub. No.:    WO/2014/178555    International Application No.:    PCT/KR2014/003441
Publication Date: 06.11.2014 International Filing Date: 21.04.2014
IPC:
A61K 31/70 (2006.01), A61K 48/00 (2006.01), A61K 38/17 (2006.01), A61K 38/16 (2006.01)
Applicants: INDUSTRY ACADEMIC COOPERATION FOUNDATION, SOOKMYUNG WOMEN'S UNIVERSITY [KR/KR]; (sookmyung Women's University, Cheongpa-dong 2(i)-ga), 100, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 140-132 (KR)
Inventors: PARK, Jong Hoon; (KR).
WOO, Yu Mi; (KR).
KIM, Young Joon; (KR).
BAE, Jae Bum; (KR).
PARK, Eun Young; (KR).
LEE, Sun Young; (KR).
SHIN, Yu Bin; (KR)
Agent: KANG, Seong Hea; (Doryong-dong), #Da-205, 530 Daedeok-daero, Yuseong-gu, Daejeon 305-340 (KR)
Priority Data:
10-2013-0047338 29.04.2013 KR
Title (EN) PHARMACEUTICAL COMPOSITION FOR ALLEVIATING OR TREATING AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE COMPRISING DNA METHYLATION INHIBITOR
(FR) COMPOSITION PHARMACEUTIQUE POUR SOULAGER OU TRAITER UNE MALADIE POLYKYSTIQUE DES REINS AUTOSOMIQUE DOMINANTE COMPRENANT UN INHIBITEUR DE METHYLATION D'ADN
(KO) DNA 메틸화 저해제를 포함하는 상염색체 우성 다낭신 개선 또는 치료용 약학 조성물
Abstract: front page image
(EN)In order to determine epigenetic variations of autosomal dominant polycystic kidney disease and functional association therebetween, the present inventors have subjected individuals with polycystic kidney disease and without polycystic kidney disease to analysis through methylation profiling in random fashion of the genome as a whole. Interestingly, in PKD1 and other genes associated with ion transport and cell adhesion, there was hypermethylation in the gene-body region, and the expression of these genes was down-regulated in polycystic kidney disease. In particular, in PKD1, there was hypermethylation in the polycystic kidney disease gene-body region, and this was associated with MBD2 (methyl-CpG-binding domain 2) protein binding. In addition, DNA methylation inhibitor treatment was accompanied by up-regulation of PKD1 expression and caused a delay in cyst formation in MDCK (Madin-Darby Canine Kidney) cells. This therefore demonstrates that, in the present invention, hypermethylation of PKD1 and regulator genes associated with cyst formation plays a decisive role in cyst formation and shows that the present invention can be used in therapeutic applications for autosomal dominant polycystic kidney disease.
(FR)Selon la présente invention, de façon à déterminer des variations épigénétiques d'une maladie polykystique des reins autosomique dominante et une association fonctionnelle entre elles, les présents inventeurs ont soumis des individus ayant une maladie polykystique des reins et sans maladie polykystique des reins à une analyse par l'intermédiaire d'un profilage de méthylation d'une manière aléatoire du génome dans sa totalité. De façon intéressante, dans les gènes PKD1 et d'autres gènes associés à un transport d'ions et à une adhésion de cellules, il y a eu une hyper-méthylation dans la région de corps de gène, et l'expression de ces gènes a été régulée à la baisse dans une maladie polykystique des reins. En particulier, dans PKD1, il y a eu une hyper-méthylation dans la région de corps de gène de maladie polykystique des reins, et ceci a été associé à une liaison de protéine MBD2 (domaine 2 de liaison à méthyl-CpG). En outre, un traitement d'inhibiteur de méthylation d'ADN a été accompagné d'une régulation à la hausse de l'expression de PKD1 et a entraîné un retard de formation de kyste dans des cellules MDCK (rein canin Madin-Darby). Ainsi ceci démontre que, dans la présente invention, l'hyper-méthylation des gènes PKD1 et de gènes de régulation associés à une formation de kyste joue un rôle décisif dans la formation de kyste et montre que la présente invention peut être utilisée dans des applications thérapeutiques pour une maladie polykystique des reins autosomique dominante.
(KO)본 발명자들은 상염색체 우성 다낭신의 후성적 변이와 그들의 기능적 관련성을 결정하기 위해 다낭신 및 비-다낭신 개체를 게놈 전체에서 무작위적으로 메틸화 프로파일링하여 분석하고 그들의 발현 데이타와 비교하였다. 흥미롭게도 이온전달 및 세포접합과 관련된 PKD1 및 다른 유전자들은 유전자 몸체 부분에서 과메틸화되었고, 그들의 발현은 다낭신에서 하향조절되었다. 특히, PKD1은 다낭신 유전자 몸체 부분에서 과메틸화되었고 이것은 MBD2 (methyl-CpG-binding domain 2) 단백질 결합과 연관되어 있었다. 뿐만 아니라, DNA 메틸화 저해제 처리는 Pkd1 발현의 상향조절을 수반하며 MDCK (Madin-Darby Canine Kidney) 세포의 낭포 형성을 지연시켰다. 따라서, 본 발명은 PKD1과 낭포형성과 관련된 조절 유전자들의 과메틸화가 낭포 형성에 있어서 결정적인 역할을 수행함을 보여주며, 상염색체 우성 다낭신의 치료용도로 이용할 수 있음을 제시한다.
Designated 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, 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.
African Regional Intellectual Property Organization (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Organization (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (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)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG).
Publication Language: Korean (KO)
Filing Language: Korean (KO)