公开(公告)号：US09834820B2

公开(公告)日：2017-12-05

申请号：US14577177

申请日：2014-12-19

申请人： INSERM (Institut National de la Sante et de la Recherche Medicale) ,  UNIVERSITE PARIS DESCARTES ,  ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (AP-HP)

发明人： Valerie Cormier-Daire ,  Arnold Munnich

IPC分类号： C12Q1/68 ,  A61K31/357 ,  A61K38/52

CPC分类号： C12Q1/6883 ,  A61K31/357 ,  A61K38/52 ,  C12Q2600/136 ,  C12Q2600/156 ,  C12Y503/99005

摘要： Described herein are methods of the treatment and diagnosis of bone mineral density related disorders. More particularly, described herein are methods of diagnosing or predicting a bone mineral density related disease, or a risk of a bone mineral density related disease, in a subject, which method comprises detecting a mutation in the TBXAS1 gene, wherein the presence of such a mutation is indicative of a bone mineral density related disease or of a risk of a bone mineral density related disease. Also described are compounds such as a thromboxane synthase (TXAS) encoding polynucleotide, a TXAS, thromboxane A2 or an analog thereof for treating or preventing a disease associated with an increased bone mineral density (e.g., Ghosal hematodiaphyseal dysplasia syndrome). Additional aspects describe an inhibitor of TBXAS1 gene expression or a thromboxane inhibitor for treating or preventing a disease associated with a decreased bone mineral density (e.g., osteoporosis).

公开(公告)号：US5859229A

公开(公告)日：1999-01-12

申请号：US627254

申请日：1996-04-03

申请人： Douglas A. Kniss

发明人： Douglas A. Kniss

IPC分类号： C12N15/09 ,  A61K31/70 ,  A61K38/00 ,  A61K48/00 ,  A61P9/08 ,  A61P11/16 ,  A61P13/02 ,  A61P15/00 ,  A61P25/00 ,  A61P29/00 ,  A61P43/00 ,  C07H21/04 ,  C12N15/113 ,  C07H21/00 ,  A61K31/74

CPC分类号： C12N15/1137 ,  C12Y114/99001 ,  C12Y503/99005 ,  A61K38/00 ,  C12N2310/315

摘要： The present invention provides a new antisense oligonucleotides for the treatment of premature labor, premature rupture of the fetal membranes, premature cervical dilation and effacement, preeclampsia, endometriosis, rheumatoid arthritis, ARDs, and glomerulitis. The drugs are antisense oligonucleotides which attenuate the expression of either the mRNA encoding the cyclooxygenase protein or the mRNA encoding the thromboxane A.sub.2 synthase protein. Once the mRNA encoding for cyclooxygenase is inhibited, the production of cyclooxygenase is inhibited thereby inhibiting the production of the cyclooxygenase products such as prostaglandins and thromboxane. Thus, the antisense oligonucleotides provide novel therapy for the treatment of diseases involving cyclooxygenase products, prostaglandins and thromboxane metabolism. Such diseases include immunological, reproductive, cardiovascular, dermatologic, central nervous system disorders in which the release of cyclooxygenase products effects the genesis and progression of the disease. A second object of the invention is to provide new reagents for the research and study of the diseases involving cyclooxygenase products.

摘要翻译： 本发明提供了用于治疗早产，胎膜过早破裂，早产儿宫颈扩张和消退，先兆子痫，子宫内膜异位症，类风湿性关节炎，ARD和肾小球炎的新型反义寡核苷酸。 这些药物是减弱编码环加氧酶蛋白的mRNA或编码血栓素A2合酶蛋白的mRNA的表达的反义寡核苷酸。 一旦编码环氧合酶的mRNA被抑制，则环氧合酶的产生被抑制，从而抑制环加氧酶产物如前列腺素和血栓烷的产生。 因此，反义寡核苷酸提供了治疗涉及环加氧酶产物，前列腺素和血栓素代谢的疾病的新疗法。 这些疾病包括免疫学，生殖学，心血管疾病，皮肤病学，中枢神经系统疾病，其中环氧合酶产物的释放影响疾病的发生和进展。 本发明的第二个目的是提供用于研究和研究涉及环氧合酶产物的疾病的新试剂。

公开(公告)号：US20150104437A1

公开(公告)日：2015-04-16

申请号：US14577177

申请日：2014-12-19

申请人： INSERM (Institut National de la Sante et de la Recherche Medicale)

发明人： Valerie Cormier-Daire ,  Arnold Munnich

IPC分类号： C12Q1/68 ,  A61K31/357 ,  A61K38/52

CPC分类号： C12Q1/6883 ,  A61K31/357 ,  A61K38/52 ,  C12Q2600/136 ,  C12Q2600/156 ,  C12Y503/99005

摘要： The present invention relates to methods of the treatment and diagnosis of bone mineral density related disorders. More particularly, the present invention relates to a method of diagnosing or predicting a hone mineral density related disease, or a risk of a bone mineral density related disease, in a subject, which method comprises detecting a mutation in the TBXAS1 gene, wherein the presence of said mutation is indicative of a bone mineral density related disease or of a risk of a bone mineral density related disease. The invention also relates to a compound selected in the group consisting of a thromboxane synthase (TXAS) encoding polynucleotide, a TXAS, thromboxane A2 or an analog thereof for treating or preventing a disease associated with an increased bone mineral density (e.g., Ghosal hematodiaphyseal dysplasia syndrome). The invention also relates to a compound selected from the group consisting of an inhibitor of TBXAS1 gene expression or a thromboxane inhibitor for treating or preventing a disease associated with a decreased bone mineral density (e.g., osteoporosis).

摘要翻译： 本发明涉及骨矿物质密度相关疾病的治疗和诊断方法。 更具体地，本发明涉及诊断或预测受试者中与骨矿物质密度相关疾病或骨矿物质密度相关疾病的风险的方法，该方法包括检测TBXAS1基因中的突变，其中存在 的所述突变指示与骨矿物质密度相关的疾病或与骨矿物质密度相关的疾病的风险。 本发明还涉及一种选自下列的化合物：由血栓烷合成酶（TXAS）编码多核苷酸，TXAS，血栓素A2或其类似物组成的组，用于治疗或预防与骨矿物质密度增加相关的疾病（例如，高原性血管造影发生不良 综合征）。 本发明还涉及选自TBXAS1基因表达抑制剂或用于治疗或预防与骨矿物质密度降低相关的疾病（例如骨质疏松症）的血栓烷抑制剂的化合物。

公开(公告)号：US20100284991A1

公开(公告)日：2010-11-11

申请号：US12746456

申请日：2008-12-05

申请人： Valerie Cormier-Daire ,  Arnold Munnich

发明人： Valerie Cormier-Daire ,  Arnold Munnich

IPC分类号： A61K38/53 ,  C12Q1/68 ,  A61K31/7052 ,  A61K31/35 ,  A61P19/08

CPC分类号： C12Q1/6883 ,  A61K31/357 ,  A61K38/52 ,  C12Q2600/136 ,  C12Q2600/156 ,  C12Y503/99005

摘要： The present invention relates to methods of the treatment and diagnosis of bone mineral density related disorders. More particularly, the present invention relates to a method of diagnosing or predicting a bone mineral density related disease, or a risk of a bone mineral density related disease, in a subject, which method comprises detecting a mutation in the TBXAS1 gene, wherein the presence of said mutation is indicative of a bone mineral density related disease or of a risk of a bone mineral density related disease. The invention also relates to a compound selected in the group consisting of a thromboxane synthase (TXAS) encoding polynucleotide, a TXAS, thromboxane A2 or an analog thereof for treating or preventing a disease associated with an increased bone mineral density (e.g., Ghosal hematodiaphyseal dysplasia syndrome). The invention also relates to a compound selected from the group consisting of an inhibitor of TBXAS1 gene expression or a thromboxane inhibitor for treating or preventing a disease associated with a decreased bone mineral density (e.g., osteoporosis).

摘要翻译： 本发明涉及骨矿物质密度相关疾病的治疗和诊断方法。 更具体地，本发明涉及诊断或预测受试者中与骨矿物质密度有关的疾病或骨矿物质密度相关疾病的风险的方法，该方法包括检测TBXAS1基因中的突变，其中存在 的所述突变指示与骨矿物质密度相关的疾病或与骨矿物质密度相关的疾病的风险。 本发明还涉及一种选自下列的化合物：由血栓烷合成酶（TXAS）编码多核苷酸，TXAS，血栓素A2或其类似物组成的组，用于治疗或预防与骨矿物质密度增加相关的疾病（例如，高原性血管造影发生不良 综合征）。 本发明还涉及选自TBXAS1基因表达抑制剂或用于治疗或预防与骨矿物质密度降低相关的疾病（例如骨质疏松症）的血栓烷抑制剂的化合物。