13 results about "Myotonic dystrophy gene" patented technology

The disclosure relates to double stranded ribonucleic acid (dsRNA) agents and compositions targeting a dystrophy myotonic protein kinase (DMPK) gene, as well as methods of inhibiting expression of a DMPK gene and methods of treating subjects having a DMPK-associated disease or disorder, e.g., myotonic dystrophy (DM), using such dsRNA agents and compositions.

The present application relates to oligonucleotides (e.g., antisense oligonucleotides such as gapmers) designed to target DMPK RNAs and targeting complexes for delivering the oligonucleotides to cells (e.g., muscle cells) and uses thereof, particularly uses relating to treatment of disease. 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 DMPK.

Delivery construct-oligonucleotide conjugates, pharmaceutical compositions, and their use for the treatment of myotonic dystrophy type 1 in a human subject are disclosed.

The present invention provides compounds of Formula I: and pharmaceutically acceptable salts thereof, compositions thereof, and methods of using the same in methods of treating diseases, disorders, and conditions such as myotonic dystrophy type 1 (DM1).

Disclosed are muscle-selective promoter combinations and RNA-targeting gene therapy compositions and methods comprising the same for treating DM1.

Disclosed are methods of treating a subject having myotonic dystrophy type 1 (DM1). The methods include administering a therapeutic regimen including a plurality of doses of a conjugate spaced at a time interval of at least 1 month, where the conjugate includes an oligonucleotide and a peptide covalently bonded or linked via a linker to the oligonucleotide, the peptide including a hydrophobic domain flanked by two cationic domains, each of the cationic domains including one of RBRRBRR (SEQ ID NO: 1), RBRBR (SEQ ID NO: 2), RBRR (SEQ ID NO: 3), RBRRBR (SEQ ID NO: 4), RRBRBR (SEQ ID NO: 5), RBRRB (SEQ ID NO: 6), BRBR (SEQ ID NO: 7), RBHBH (SEQ ID NO: 8), HBHBR (SEQ ID NO: 9), RBRHBHR (SEQ ID NO: 10), RBRBBHR (SEQ ID NO: 11), RBRRBH (SEQ ID NO: 12), HBRRBR (SEQ ID NO: 13), HBHBH (SEQ ID NO: 14), BHBH (SEQ ID NO: 15), BRBSB (SEQ ID NO: 16), BRB[Hyp]B (SEQ ID NO: 17), R[Hyp]H[Hyp]HB (SEQ ID NO: 18), and R[Hyp]RR[Hyp]R (SEQ ID NO: 19), and the hydrophobic domain including one of YQFLI (SEQ ID NO: 20), FQILY (SEQ ID NO: 21), ILFQY (SEQ ID NO: 22), FQIY (SEQ ID NO: 23), VWVW, WWPWW (SEQ ID NO: 24), WPWW (SEQ ID NO: 25), and VWVPW (SEQ ID NO: 26); and the oligonucleotide including a total of 12 to 40 contiguous nucleobases, where at least 9 contiguous nucleobases are complementary to a CUG repeat sequence.

The present disclosure provides the use of compounds of Formulae (I), (II), (III), (III-A), and (III-B) (e.g., metformin) in treating a neurological disease associated with repeat expansions and / or RAN protein accumulation, reducing the level of one or more repeat associated non-ATG (RAN) proteins, and reducing the accumulation of RAN proteins in a subject and / or biological sample. Also provided is the use of compounds of Formulae (I), (II), (III), (III-A), and (III-B) (e.g., metformin) in inhibiting RAN protein translation in a subject and in a biological sample (e.g., cells, tissue). Also provided in the present disclosure are pharmaceutical compositions, kits, and uses of compounds of Formulae (I), (II), (III), (III-A), and (III-B) (e.g., metformin) for treating diseases associated with repeat expansions. Exemplary diseases associated with repeat expansions include, but are not limited to, C9ORFf72 amyotrophic lateral sclerosis (ALS), or C9ORFf72 frontotemporal dementia; myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2); spinocerebellar ataxia; Huntington's disease; Fragile X Tremor Ataxia Syndrome (FXTAS); and Fragile XE syndrome (FRAXE).

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., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

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., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

RNAi molecules for treating myotonic dystrophy type 1 (DM1) are provided herein. Furthermore, expression cassettes, vectors (e.g., rAAV), viral particles, and pharmaceutical compositions containing RNAi are provided herein. Moreover, methods and kits related to the use of RNAi for treating DM1, for example, are provided herein.

Provided herein, in certain aspects, are pharmaceutical compositions comprising an HSA-IGF2 fusion protein formulated for subcutaneous administration. As provided herein, are methods of treating muscle disorders, including myotonic dystrophies, comprising administration of a pharmaceutical composition comprising an HSA-IGF2 fusion protein formulated for subcutaneous administration.

This application relates to oligonucleotides designed to target DMPK RNA (e.g., antisense oligonucleotides such as gapmer), targeted conjugates for delivering oligonucleotides to cells (e.g., muscle cells), and their uses, particularly in relation to the treatment of diseases. [Solution] In some embodiments, the muscle targeting agent specifically binds to internalized cell surface receptors on muscle cells. In some embodiments, the molecular payload inhibits the expression or activity of DMPK.

Disclosed are antagonists of human microRNA miR-100, miR-20, miR-222, miR-181, and miR-92 and uses of same. The invention provides inhibitors of human microRNA miR-100, miR-20a, miR-222, miR-181c, and miR-92a, which are repressors of the genes MBNL1 and / or MBNL2. The use of the inhibitors as a drug, in particular against myotonic dystrophy type 1, is also provided.