9127results about "Neuromuscular disorder" patented technology

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

To provide a medicine for treating a disease in a mammal.SOLUTION: Provided is a medicine for treating a disease in a mammal, comprising an expression cassette that is a first expression cassette comprising a chimeric gene operably linked to a first expression control element, the chimeric gene comprising a first portion comprising a minigene having an alternatively spliced exon and a second portion encoding a first RNA encoding a protein, the first portion being 5' to the second portion, the second portion lacking an initiation codon or start codon, the alternatively spliced exon comprising a translation initiation regulatory sequence, expression of the protein being controlled by inclusion of the alternatively spliced exon, and the medicine being used in combination with a small molecule splicing modifier that modulates splicing of the alternatively spliced exon.SELECTED DRAWING: Figure 1

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., an RNAi oligonucleotide such as an siRNA, useful for targeting DUX4) covalently linked to an antibody (e.g., anti-TfRl antibody).

Aspects of the disclosure relate to methods of reducing fatigue in a subject having myotonic dystrophy type 1 (DM1). Aspects of the disclosure relate to methods of treating one or more symptoms assessable by the MDHI (e.g., a GI symptom, myotonia, upper extremity function impairment, fatigue, mobility impairment, impairment in the ability to perform activities, pain, vision impairment, communication impairment, sleep impairment, emotional issues, cognitive impairment, social satisfaction impairment, social performance impairment, breathing impairment, swallowing impairment, and / or hearing impairment) in a subject having myotonic dystrophy type 1 (DM1). In some embodiments, the methods comprise administering to the subject a composition comprising complexes (e.g., muscle targeting complexes) comprising an oligonucleotide (e.g., a DMPK- targeting oligonucleotide) covalently linked to an antibody (e.g., anti-TfRl antibody).

Aspects of the disclosure relate to compositions comprising a plurality of complexes comprising an antibody (e.g., anti-TfRI antibody) covalently linked to one or more oligonucleotides (e.g. a DMPK targeting oligonucleotide), each oligonucleotide being covalently linked at a linkage site represented by a lysine (K) residue of the antibody. In some embodiments, the antibody comprises a heavy chain comprising a heavy chain variable region (VH) and a heavy chain constant region, and a light chain comprising a light chain variable region (VL) and a light chain constant region, wherein at least 80% (e.g., 80%-98%, 80%-95%, 80%-90%, 85%-98%, 85%-95%, 85%-90%, 90%-98%, 90%-95%, 95%-97%, or more) of the light chain constant regions of the antibodies of the complexes in the composition are independently covalently linked to an oligonucleotide at a linkage site represented by K188 (based on Kabat numbering) and / or a linkage site represented by K190 (based on Kabat numbering) of the light chain constant regions of the antibodies.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Aspects of the disclosure relate to methods of reducing expression or activity of DMPK (e.g., reducing the level of a mutant or wild-type DMPK RNA, or the activity of a DMPK gene product) and / or methods of treating myotonic dystrophy (e.g., DM1) in a subject. In some embodiments, the methods comprise administering to the subject a composition comprising complexes (e.g., muscle targeting complexes) comprising an oligonucleotide (e.g., a DMPK—targeting oligonucleotide) covalently linked to an antibody (e.g., anti-TfR1 antibody).

To provide a compound which is a novel proline derivative, and to provide a pharmaceutical composition comprising the compound for the treatment of, for example, systemic sclerosis (SSc) and non-alcoholic steatohepatitis (NASH).SOLUTION: A pharmaceutical composition comprises, as a cGAS inhibitor, a compound which is a novel proline derivative encompassed by formula (I), or a prodrug, a pharmaceutically acceptable salt, or a stereoisomer of the compound.SELECTED DRAWING: None

To provide a mitochondria function-improving agent or the like which improves a mitochondria function in a skin cell.SOLUTION: A mitochondria function-improving agent that improves a mitochondria function in a cell contains components included in a swallow's nest as an active ingredient. According to each point of view of the present invention, a mitochondria function-improving agent or the like which improves mitochondria function in a skin cell can be provided.SELECTED DRAWING: Figure 3

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotidic linkages and patterns thereof and are useful for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping exon 52 of dystrophin (DMD) transcripts. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders or diseases including Duchenne muscular dystrophy.

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotidic linkages and patterns thereof and are useful for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping exon 44 of dystrophin (DMD) transcripts. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders or diseases including Duchenne muscular dystrophy.

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or intemucleotidic linkages and patterns thereof and are useful for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping exon 45 of dystrophin (DMD) transcripts. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders or diseases including Duchemie muscular dystrophy.

The invention provides a modified TnpB-omega RNA gene editing system and application of the modified TnpB-omega RNA gene editing system. In particular, the present invention provides a modified TnpB related [omega] RNA skeleton. The modified omega RNA skeleton provided by the invention has at least three stem-loop structure fragments, and has a shorter length and a compact structure than a natural omega RNA skeleton, so that the modified omega RNA skeleton and TnpB can be jointly carried in a single AAV vector, the administration efficiency is improved, and high-efficiency gene editing is realized.

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, the present disclosure provides technologies useful for exon skipping in cell populations, e.g., myocyte stem cells. In some embodiments, the present disclosure provides technologies useful for restoring functioning of myocyte stem cells. In some embodiments, the present disclosure provides technologies useful for regeneration of myocyte stem cells. In some embodiments, the present disclosure provides technologies useful for differentiation of myocyte stem cells. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders, or diseases including Duchenne muscular dystrophy.

The invention relates to the technical field of a preparation method of a type A recombinant botulinum toxin, in particular to a type A botulinum toxin obtained by adopting a gene recombination technology, and the amino acid sequence of the type A botulinum toxin is consistent with the sequence of the type A botulinum toxin prepared by extracting and purifying a wild strain Clostridium botulinum. According to the technical scheme, the single-chain protein of the botulinum toxin A sequentially comprises a botulinum toxin A light chain or a modified botulinum toxin A light chain, a connecting region and a botulinum toxin A heavy chain. According to the scheme, the high-quality recombinant botulinum toxin A is obtained after the single-chain protein is subjected to fermentation, crude purification, enzyme digestion and fine purification. According to the technical scheme, the problems of complex process, long period, high safety risk and the like in the existing process for preparing the botulinum toxin A from the wild bacterial strain clostridium botulinum can be solved, and meanwhile, the problem that the amino acid sequence consistent with that of the botulinum toxin A prepared from the wild bacterial strain clostridium botulinum cannot be obtained through the existing gene recombination technology is solved.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle dystrophy (DM1).

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Composition containing Nicotinamide and vitamin B6 are provided. The composition may be an oral nutritional composition, for example a nutritional supplement, an oral nutritional supplement, a food product, a food for special medical purpose (FSMP). The composition can be administered to an individual in need thereof for treating muscle injury, and / or promoting muscle repair, improving skeletal muscle regeneration, maintaining or increasing skeletal muscle function and / or skeletal muscle mass in an individual with muscle injury.

Among other things, the present disclosure provides various technologies including chirally controlled oligonucleotide compositions and technologies for manufacturing and using such oligonucleotide compositions. In some embodiments, the present disclosure provides technologies useful for preventing or treating various conditions, disorders or diseases, e.g., Duchenne Muscular Dystrophy.

The invention provides compositions comprising a source of protein and a urolithin. The invention also provides uses and methods associated with, or making use of the compositions, such as a medicament, dietary supplement, functional food or medical food and in the treatment and / or prophylaxis of a muscle-related pathological condition. The invention also provides kits comprising urolithin and protein.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a disease allele associated with muscle disease. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.