The present invention relates to the treatment of muscular diseases.

The present invention provides a conjugate of an oligonucleotide having a nucleic acid sequence expected to have a pharmacological effect in hepatic parenchymal cells with a biantennary GalNAc unit, or a pharmaceutically acceptable salt thereof, and a medicament or the like containing the same as an active component.

Compositions and methods for treating diseases and conditions mediated by the high affinity IgE receptor (FcεRI) are provided. Also provided are antisense oligomers for modulating splicing of mRNA encoding a MS4A6A protein, optionally in addition to antisense oligomers for modulating splicing of mRNA encoding the FcεRIβ protein, thereby down-regulating cell-surface expression of FcεRI, and uses of the antisense oligomers for inhibiting mast cell degranulation, cytokine release, migration, and proliferation; for inhibiting anaphylaxis reactions in individuals, for treating allergic conditions in individuals, for reducing the incidence of allergic reactions in individuals, for treating individuals at risk of developing anaphylactic reactions, and for treating mast cell-related diseases in individuals.

Disclosed are a 5′-modified nucleoside and a nucleotide using the same. The nucleoside of the present invention is represented by the formula (I) below. The 5′-modified nucleoside of the present invention is usable as a substitute for a phosphorothioate-modified nucleic acid, which has a risk of, for example, accumulation in a specific organ. The 5′-modified nucleoside also has excellent industrial productivity because a diastereomer separation step is not involved in the production process thereof.

##STR00001##

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 53 skipping are described.

The present disclosure relates to modified antisense oligonucleotides. The nucleotides described herein are of 10 to 40 nucleobases and include a targeting sequence complementary to a target region within intron 1 of a pre-mRNA of the human alpha glucosidase (GAA) gene. The target region includes at least one additional nucleobase compared to the targeting sequence, wherein the at least one additional nucleobase has no complementary nucleobase in the targeting sequence, and wherein the at least one additional nucleobase is internal to the target region.

Antisense oligomers complementary to a selected target site in the human dystrophin gene to induce exon 2 skipping are described. In various aspects, antisense oligomers are described according to Formula (I): Formula (I) or a pharmaceutically acceptable salt thereof, wherein T, Nu, n, and R.sup.100 are defined herein.

##STR00001##

The present invention aims at establishing a novel therapy for facioscapulohumeral muscular dystrophy.

An oligonucleotide or a pharmaceutically acceptable salt thereof, wherein the oligonucleotide comprises an oligonucleotide of 15-30 bases consisting of a nucleotide sequence complementary to the region of nucleotide Nos. 502-556 or 578-612 of DUX4-fl mRNA consisting of the nucleotide sequence as shown in SEQ ID NO: 1; the 5′ and/or 3′ end of the oligonucleotide may be chemically modified; and the oligonucleotide is capable of switching the splice form of the DUX4 gene from DUX4-fl to DUX4-s. A pharmaceutical drug comprising the above oligonucleotide or a pharmaceutically acceptable salt thereof (e.g. therapeutic for facioscapulohumeral muscular dystrophy).

The present invention provides the peptide nucleic acid derivative which targets 3′ splice site of the human MLPH pre-mRNA “exon 2”. The peptide nucleic acid derivatives in the present invention strongly induce splice variants of the human MLPH mRNA in cell and are very useful to treat diseases or conditions of skin pigmentation associated with the human MLPH protein.

The present invention concerns the use of antisense oligonucleotides (AON) capable of inhibiting expression of dynamin 2, advantageously human dynamin 2, for use in the treatment of Charcot-Marie-Tooth disease (CMT) and centronuclear myopathies (CNM).