59 results about "Myotonic dystrophy gene" patented technology

An antisense compound for use in treating myotonic dystrophy DM1 or DM2, a method of enhancing antisense targeting to heart and quadricep muscles, and a method for treating DM1 or DM2 in a mammalian subject are disclosed. The oligonucleotide has 8-30 bases, with at least 8 contiguous bases being complementary to the polyCUG or polyCCUG repeats in the 3′UTR region of dystrophia myotonica protein kinase (DMPK) mRNA in DM1 or DM2, respectively. Conjugated to the oligonucleotide is a cell-penetrating peptide having the sequence (RXRR(B / X)R)2XB, where R is arginine; B is β-alanine; and each X is —C(O)—(CH2)n—NH—, where n is 4-6. The antisense compound is effective to selectively block the sequestration of muscleblind-like 1 protein (MBNL1) and / or CUGBP, in heart and quadricep muscle in a myotonic dystrophy animal model.

Provided are tricyclo-DNA (tc-DNA) AON and methods employing tc-DNA AON for modifying splicing events that occur during pre-mRNA processing. Tricyclo-DNA (tc-DNA) AON are described that may be used to facilitate exon skipping or to mask intronic silencer sequences and / or terminal stem-loop sequences during pre-mRNA processing and to target RNase-mediated destruction of processed mRNA. Tc-DNA AON described herein may be used in methods for the treatment of Duchenne Muscular Dystrophy by skipping a mutated exon 23 or exon 51 within a dystrophin gene to restore functionality of a dystrophin protein; in methods for the treatment of Spinal Muscular Atrophy by masking an intronic silencing sequence and / or a terminal stem-loop sequence within an SMN2 gene to yield modified functional SMN2 protein, including an amino acid sequence encoded by exon 7, which is capable of at least partially complementing a non-functional SMN1 protein; and in methods for the treatment of Steinert's Myotonic Dystrophy by targeting the destruction of a mutated DM1 mRNA comprising 3′-terminal CUG repeats.

An antisense compound for use in treating myotonic dystrophy DM1 or DM2, a method of enhancing antisense targeting to heart and quadricep muscles, and a method for treating DM1 or DM2 in a mammalian subject are disclosed. The oligonucleotide has 8-30 bases, with at least 8 contiguous bases being complementary to the polyCUG or polyCCUG repeats in the 3′UTR region of dystrophia myotonica protein kinase (DMPK) mRNA in DM1 or DM2, respectively. Conjugated to the oligonucleotide is a cell-penetrating peptide having the sequence (RXRR(B / X)R)2XB, where R is arginine; B is β-alanine; and each X is —C(O)—(CH2)n—NH—, where n is 4-6. The antisense compound is effective to selectively block the sequestration of muscleblind-like 1 protein (MBNL1) and / or CUGBP, in heart and quadricep muscle in a myotonic dystrophy animal model.

Disclosed are RNA targeting compounds having the formula:wherein j is an integer from 1 to 100; each i is the same or different and is zero or an integer from 1 to 100; each Z1 represents the same or different linking moiety; each R1 is the same or different and represents an alkyl group or an aryl group; each Q1 represents the same or different RNA binding ligand; Q2 is an alkyl group; Q3 is a halogen, an alkyl group, an aryl group, or an amine. Also disclosed are RNA targeting compounds that include a polymer backbone and two or more pendant RNA binding ligands that are bound to the polymer backbone. Methods for using the subject RNA targeting compounds to treat myotonic dystrophy and other diseases are also disclosed, as are compounds that can be used to prepare the subject RNA targeting compounds.

The disclosure provides novel conjugates comprising antisense oligonucleotides that hybridize to a DMPK transcript and a 3E10 antibody or binding fragment thereof. Also considered are these conjugates further comprising MBNL1 polypeptides. Methods of treating myotonic dystrophy using these conjugates and kits comprising these conjugates are also considered. Wherein the conjugates are suitable for delivery to muscle cells.

An antisense compound for use in treating myotonic dystrophy DM1 or DM2, a method of enhancing antisense targeting to heart and quadricep muscles, and a method for treating DM1 or DM2 in a mammalian subject are disclosed. The oligonucleotide has 8-30 bases, with at least 8 contiguous bases being complementary to the polyCUG or polyCCUG repeats in the 3′UTR region of dystrophia myotonica protein kinase (DMPK) mRNA in DM1 or DM2, respectively. Conjugated to the oligonucleotide is a cell-penetrating peptide having the sequence (RXRR(B / X)R)2XB, where R is arginine; B is β-alanine; and each X is —C(O)—(CH2)n—NH—, where n is 4-6. The antisense compound is effective to selectively block the sequestration of muscleblind-like 1 protein (MBNL1) and / or CUGBP, in heart and quadricep muscle in a myotonic dystrophy animal model.

The disclosure provides novel conjugates comprising antisense oligonucleotides that hybridize to a DMPK transcript and a 3E10 antibody or binding fragment thereof. Also considered are these conjugates further comprising MBNL1 polypeptides. Methods of treating myotonic dystrophy using these conjugates and kits comprising these conjugates are also considered. Wherein the conjugates are suitable for delivery to muscle cells.

The disclosure provides novel conjugates comprising antisense oligonucleotides that hybridize to a DMPK transcript and a 3E10 antibody or binding fragment thereof. Also considered are these conjugates further comprising MBNL1 polypeptides. Methods of treating myotonic dystrophy using these conjugates and kits comprising these conjugates are also considered. Wherein the conjugates are suitable for delivery to muscle cells.

Stem cells, stem cell lines and differentiated cells, tissues and organs which carry disease-causing mutations are provided. There is also provided a method of identifying agents suitable for treating disorders associated with at least one disease-causing mutations such as myotonic dystrophy and van Waardenburg syndrome.

The invention provides compounds, compositions and methods for treating myotonic dystrophy. The compounds can selectively bind to CUG repeats in RNA, or to CTG repeats in DNA, and inhibit replication of the nucleic acids.

Disclosed is a compound for treatment of Myotonic Dystrophy type 1 having the formula:Wherein X is selected from the group consisting of O, N, C, or S, Y is a homo- or heteroatomic 5-membered ring comprising one or more atoms selected from the group consisting of N, O, S, and C, Z is an optionally substituted aryl group or optionally substituted heteroaryl, including but not limited to halogenated benzenes, pyridines, substituted benzene, substituted pyridine, R2=hydroxy, acyl, alkoxyl, esters, ethers, cyclic ethers, and lactones, R3=H, alkyl, an optionally substituted alkyl, aliphatic ether, ester, cyclic unsaturated and aromatic ring groups, and R1, R4 and R5 are independently selected from the group consisting of hydrogen, halogen, alkyl, and alkoxyl or a pharmaceutically or cosmetically acceptable salt, solvate, or hydrate thereof.

In certain embodiments, the present invention provides compositions and methods for treating myotonic dystrophy.

In certain embodiments, the present invention provides compositions and methods for treating myotonic dystrophy.

The invention provides rationally designed multi-targeting therapeutic agents for myotonic dystrophy type 1 (DM1), an incurable neuromuscular disease that originates in an abnormal expansion of CTG repeats (CTGexp) in the DMPK gene. The rationally designed small molecules target the DM1 pathobiology in three distinct ways: (1) binding the expanded trinucleotide repeat, CTGexp, and inhibiting its transcription to the toxic CUGexp RNA, (2) binding the CUGexp RNA and releasing sequestered muscleblind-like protein (MBNL1), and (3) cleaving the toxic CUGexp in an RNase-like manner. Importantly, the compounds can reduce the levels of CUGexp in DM1 model cells and reverse two separate CUGexp-induced phenotypes of DM1.

Methods of improving neurodegenerative disease with CCR3 modulating agents are provided. The methods include administering a therapeutically effective amount of the CCR3 modulating agent to the subject, with a concomitant improvement in cognition, motor, or other neurodegenerative-affected function. Cognitive and motor diseases upon which the methods of the invention can improve cognition include Alzheimer's disease, Parkinson's disease, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, glaucoma, myotonic dystrophy, vascular dementia, progressive supranuclear palsy.

The present invention relates to compositions and methods for the treatment of nucleotide repeat expansion disorders such as myotonic dystrophy.

This invention related to compounds that are inhibitors of the CDK12 kinase. The compounds are useful in the treatment of disorders mediated by the CDK12 kinase including myotonic dystrophy type 1 (DM1) and other disorders caused by the generation of RNA repeat expansion transcripts. In particular, the invention relates to compounds of the formula (I), or a pharmaceutically acceptable salts or N-oxides thereof, wherein R1a, R2, R3, R4a, R4b and R4c are as defined herein.

Provided herein are peptide-linked morpholino (PPMO) antisense oligonucleotides that target the poly CUG repeat tract in the 3' untranslated region of the gene encoding dystrophia myotonica-protein kinase (DMPK) and methods for systemic administration of the same for the treatment of mytonic dystrophy type I (DM1).

The present invention relates to a method for diagnosing myotonic dystrophy type 1 or a method for identifying myotonic dystrophy type 1 patients by using a computer processor. The method of the present invention is an early diagnosis method of a genetic disorder having no effective prevention method except prevention in the early months of pregnancy, and can be applied to a method for diagnosing various dominant or recessive genetic disorders in which a specific repeating base sequence of a specific gene is abnormal. According to the method of the present invention, it is possible to take suitable measures related to symptoms, which will occur later, by classifying a genetic carrier and first to third risk groups according to the repetition number of the CTF sequence of 3'-noncoding region of the DDMPK gene. Particularly, the method of the present invention numerically provides a genetic carrier or the approximate prevalence of a disease with respect to an unborn baby, thereby allowing the risk of disorders to be accurately understood.

The present invention relates to methods and compositions for the treatment of Myotonic Dystrophy type 1 (DM1) with an AMPK activator <eq.metformin or troglizazone>.

Disclosed are RNA targeting compounds, methods for using the subject RNA targeting compounds to treat myotonic dystrophy and other diseases are also disclosed.

The present invention relates to improvement of epithelial or endothelial barrier function by increasing a level of myotonic dystrophy kinase-related Cdc42-binding kinases a (MRCKalpha) in one or more cells in the barrier.

Provided are tricyclo-DNA (tc-DNA) AON and methods employing tc-DNA AON for modifying splicing events that occur during pre-mRNA processing. Tricyclo-DNA (tc-DNA) AON are described that may be used to facilitate exon skipping or to mask intronic silencer sequences and / or terminal stein-loop sequences during pre-mRNA processing and to target RNase-mediated destruction of processed mRNA. Tc-DNA AON described herein may be used in methods for the treatment of Duchenne Muscular Dystrophy by skipping a mutated exon 23 or exon 51 within a dystrophin gene to restore functionality of a dystrophin protein; in methods for the treatment of Spinal Muscular Atrophy by masking an intronic silencing sequence and / or a terminal stem-loop sequence within an SMN2 gene to yield modified functional SMN2 protein, including an amino acid sequence encoded by exon 7, which is capable of at least partially complementing a non-functional SMN1 protein; and in methods for the treatment of Steinert's Myotonic Dystrophy by targeting the destruction of a mutated DM1 mRNA comprising 3′-terminal CUG repeats.

The present invention relates to caffeine for use in the treatment of myotonic dystrophy type 1 and type 2. The present invention also relates to compositions comprising caffeine for use in the treatment of myotonic dystrophy type 1 and type 2.

The present invention relates to compositions and methods for the treatment of myotonic dystrophy.

The invention provides rationally designed multi-targeting therapeutic agents for myotonic dystrophy type 1 (DM1), an incurable neuromuscular disease that originates in an abnormal expansion of CTG repeats (CTGexp) in the DMPK gene. The rationally designed small molecules target the DM1 pathobiology in three distinct ways: (1) binding the expanded trinucleotide repeat, CTGexp, and inhibiting its transcription to the toxic CUGexp RNA, (2) binding the CUGexp RNA and releasing sequestered muscleblind-like protein (MBNL1), and (3) cleaving the toxic CUGexp in an RNase-like manner. Importantly, the compounds can reduce the levels of CUGexp in DM1 model cells and reverse two separate CUGexp-induced phenotypes of DM1.

Methods of improving neurodegenerative disease with CCR3 modulating agents are provided. The methods include administering a therapeutically effective amount of the CCR3 modulating agent to the subject, with a concomitant improvement in cognition, motor, or other neurodegenerative-affected function. Cognitive and motor diseases upon which the methods of the invention can improve cognition include Alzheimer's disease, Parkinson's disease, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, glaucoma, myotonic dystrophy, vascular dementia, progressive supranuclear palsy.

The invention provides a novel DMPK isoform, isolated and purified RNA encoding the novel isoform, and methods of detecting the novel isoform, e.g., to predict disease outcome or detect disease.

The disclosure features compositions and methods for the treatment of disorders associated with improper ribonucleic acid (RNA) splicing, including disorders characterized by nuclear retention of RNAtranscripts containing aberrantly expanded repeat regions that bind and sequester splicing factor proteins. Disclosed herein are interfering RNA constructs that suppress the expression of RNA transcripts containing expanded repeat regions, as well as viral vectors, such as adeno-associated viral vectors, encoding such interfering RNA molecules. For example, the disclosure features interfering RNAmolecules, such as siRNA, miRNA, and shRNA constructs, that anneal to dystrophia myotonica protein kinase (DMPK) RNA transcripts and attenuate the expression of DMPK RNA containing expanded CUG trinucleotide repeats. Using the compositions and methods described herein, a patient having an RNA dominance disorder, such as a human patient having myotonic dystrophy, among other conditions described herein, may be administered an interfering RNA construct or vector containing the same so as to reduce the occurrence of spliceopathy in the patient, thereby treating an underlying etiology of the disease.