Other

Daiichi Sankyo Company, Limited

Orphan Disease Treatment Institute Co., Ltd.

Knc Laboratories Co., Ltd.

Kobe Gakuin Educational Foundation

The University of Tokyo

Microbial Chemistry Research Foundation

Nonprofit Organization Translational Research Organization of Duchenne Muscular Dystrophy

Takeshima, Yasuhiro

Matsuo, Masafumi

Masafumi Matsuo

Makoto Koizumi

Yasuhiro Takeshima

Atsushi Nishida

Yoshikazu Takahashi

Takeshi Masuda

Kentaro Ito

Masatoshi Hagiwara

Daishiro Ikeda

Yoshiyuki Onishi

Mitsuhiro Iwamoto

Ryoichi Matsuda

Shinnosuke Tsuji

Yukiko Sekiguchi

Koji Ikeda

Shoichiro Kamei

Masataka Shiozuka

Mitsuhiro Yokoyama

Yoshiaki Nonomura

Seiji Matsuda

Kazuhiro Maeta

Akira Wagatsuma

Naoyuki Kataoka

Noriaki Emoto

Sunu Budhi Raharjo

Yudha Nurhantari

Kayoko Saiki

Kosuke Okazaki

A method of inhibiting myostatin signaling via a myostatin splice variant-derived protein is provided. The protein and an expression system thereof are applicable to therapy for diseases in which myostatin is involved.

Inhibition of myostatin signal by myostatin splice variant-derived protein and utilization thereof

The present invention establishes a molecular therapy for glycogen storage disease type Ia. The present invention provides an oligonucleotide of 15-30 bases comprising a nucleotide sequence complementary to die cDNA of G6PC gene with c.648G>T mutation, wherein the oligonucleotide comprises a sequence complementary to a region comprising any site between the 82to the 92nucleotide from the 5′ end of exon 5 of the G6PC gene with c.648C>T mutation, a pharmacologically acceptable salt or solvate thereof. Also provided is a pharmaceutical drug comprising the oligonucleotide, a pharmacologically acceptable salt or solvate thereof (e.g., therapeutic drug for glycogen storage disease type Ia).

Therapeutic agent for glycogen storage disease type IA

Insertion of variant exons of CD44 gene of cancer stem cells into its mRNA is inhibited whereupon the cancer stem cells lose their properties so that they are rendered sensitive to anticancer agents and radiation, possibly leading to cancer treatment. A drug for cancer treatment, comprising an antisense oligonucleotide capable of inducing skipping of variant exon(s) of CD44 gene to thereby increase expression of normal CD44 mRNA, a pharmaceutically acceptable salt thereof, a solvate thereof or a prodrug thereof. An oligonucleotide of 20-23 bp having the entirety or a part of any one of the nucleotide sequences as shown in SEQ ID NOS: 1 to 19, a pharmaceutically acceptable salt thereof, a solvate thereof or a prodrug thereof. A drug for inducing skipping of at least one variant exon selected from the group consisting of variant exons 8, 9 and 10 of CD44 gene, comprising the above-described oligonucleotide, a pharmaceutically acceptable salt thereof, a solvate thereof or a prodrug thereof.

Nucleic acid drug for inducing skipping of variant exon of CD44 gene and increasing expression of normal type CD44 mRNA

Oligonucleotides having a nucleotide sequence complementary to nucleotide numbers such as 2571-2607, 2578-2592, 2571-2592, 2573-2592, 2578-2596, 2578-2601 or 2575-2592 of the dystrophin cDNA (Gene Bank accession No. NM_004006.1) and therapeutic agents for muscular dystrophy comprising such oligonucleotides.

ENA nucleic acid pharmaceuticals capable of modifying splicing of mRNA precursors

A readthrough inducing agent for inducing readthrough of a premature stop codon generated by nonsense mutations, the readthrough inducing agent comprising a compound having a structure expressed by the following Structural Formula (A), and a drug for treating a genetic disease caused by nonsense mutations, the drug comprising the readthrough inducing agent. 

Readthrough inducing agent and drug for treating genetic disease caused by nonsense mutation

An object of the present invention is to provide a prophylactic or ameliorating agent for a genetic disease that is caused by a mutation in an exon of a gene and is capable of forming a functional truncated protein by skipping of the exon comprising the mutation. The prophylactic or ameliorating agent used in the present invention is a prophylactic or ameliorating agent for a genetic disease that is caused by a mutation in an exon of a gene and is capable of forming a functional truncated protein by skipping of the exon comprising the mutation, wherein the prophylactic or ameliorating agent contains a compound having a molecular weight of 1500 or lower.

Prophylactic or ameliorating agent for genetic diseases

ENA nucleic acid drugs modifying splicing in mRNA precursor

The invention provides an isolated and purified DNA set forth as SEQ ID NO:15 in the Sequence Listing and an antisense oligonucleotide complementary to the DNA. The DNA represents the splicing enhancer sequence (SES) in exon 45 of human dystrophin gene, and serves as a template in preparation of the antisense oligonucleotide, which is used to induce exon 45 skipping in certain group of patient with Duchenne muscular dystrophy to restore the reading frame of dystrophin mRNA.

Pharmaceutical composition for treatment of Duchenne muscular dystrophy

Antisense oligonucleotides comprising a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO:1 or NO:2 are disclosed. The antisense oligonucleotides are used for treatment of specific types of Duchenne muscular dystrophy which is attributed to a change in number of the nucleotides composing one or more exons adjacent to exon 43 or 53, respectively, in human dystrophin mRNA, wherein the change is due to deletion of one or more nucleotides from the normal nucleotide sequence for the exons, wherein the net of the change in number of the nucleotides is expressed as a reduction of (3&times;N&plus;1) nucleotides, wherein N is zero or a natural number.

Medicament for treatment of Duchenne muscular dystrophy

A therapeutic pharmaceutical composition for patients of Duchenne muscular dystrophy with entire loss of exon 20 in dystrophin mature mRNA is provided. The composition comprise as an active principle an antisense oligonucleotide consisting of a 20 to 50-nucleotide sequence against exon 19 of the dystrophin pre-mRNA.

Pharmaceutical composition for treatment of duchenne muscular dystrophy

Disclosed are metalloprotease proteins or their salts usable for treatment or prophylaxis of conformational diseases and for providing a screening kit for selection of carcinostatics and anti-metastatic agents. The metalloprotease proteins have an amino acid sequence set forth under SEQ ID NO:1 or NO:2 in the Sequence Listing. The proteins have a neutral optimal pH, hydrolyze endothelin 1, atrial natriuretic peptide and angiotensin I and are inhibited by 1,10-phenanthroline, phosphoramidon and thiorphan.

Membrane-bound metalloprotease and soluble secreted form thereof

Growing community of inventors

Kobe, Japan

Masafumi Matsuo