93 results about "Duchenne's Muscular Dystrophy" patented technology

Molecules are provided for inducing or facilitating exon skipping in forming spliced mRNA products from pre-mRNA molecules in cells. The molecules may be provided directly as oligonucleotides or expression products of vectors that are administered to a subject. High rates of skipping can be achieved. High rates of skipping reduce the severity of a disease like Duchene Muscular Dystrophy so that the disease is more like Becker Muscular Dystrophy. This is a severe reduction in symptom severity and mortality.

Molecules are provided for inducing or facilitating exon skipping in forming spliced mRNA products from pre-mRNA molecules in cells. The molecules may be provided directly as oligonucleotides or expression products of vectors that are administered to a subject. High rates of skipping can be achieved. High rates of skipping reduce the severity of a disease like Duchene Muscular Dystrophy so that the disease is more like Becker Muscular Dystrophy. This is a severe reduction in symptom severity and mortality.

The invention relates to glycoside-compound conjugates for use in antisense strategies and / or gene therapy. The conjugates comprise a glycoside linked to a compound, in which the glycoside is a ligand capable of binding to a mannose-6-phosphate receptor of a muscle cell. For example the cells are muscle cells of a Duchenne Muscular Dystrophy (DMD) patient and the conjugate comprises an antisense oligonucleotide which causes ex on skipping and induces or restores the synthesis of dystrophin or variants thereof.

The invention relates a method wherein a molecule is used for inducing and / or promoting skipping of at least one of exon 43, exon 46, exons 50-53 of the DMD pre-mRNA in a patient, preferably in an isolated cell of a patient, the method comprising providing said cell and / or said patient with a molecule. The invention also relates to said molecule as such.

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.

The invention relates to a method for inducing or promoting skipping of exon 45 of DMD pre-mRNA in a Duchenne Muscular Dystrophy patient, preferably in an isolated (muscle) cell, the method comprising providing said cell with a molecule that binds to a continuous stretch of at least 21 nucleotides within said exon. The invention further relates to such molecule used in said method.

This invention relates, e.g., to a method for enhancing exon skipping in a pre-mRNA of interest, comprising contacting the pre-mRNA with an effective amount of a small molecule selected from the compounds shown in Table 1, or a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof, and, optionally, with an antisense oligonucleotide that is specific for a splicing sequence in the pre-mRNA Methods for treating Duchenne muscular dystrophy (DMD) are disclosed.

The present invention provides a series of novel dystrophin minigenes that retain the essential biological functions. The expression of the dystrophin minigenes may be controlled by a regulatory element along with a small polyadenylation signal. The entire gene expression cassettes may be readily packaged into a viral vector, preferably an AAV vector. The present invention further defines the minimal functional domains of dystrophin and provides ways to optimize and create new versions of dystrophin minigenes. Finally, the present invention provides a method of treatment for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD).

Embodiments of the present invention are directed generally to antisense compounds and compositions for the treatment of muscular dystrophy, and in particular, Duchenne muscular dystrophy (DMD). In one embodiment, the invention is directed to antisense oligonucleotide molecules, pharmaceutical compositions and formulations comprising antisense oligonucleotide molecules, and methods of treating muscular dystrophy related diseases and disorders wherein the antisense oligonucleotide molecules comprises a base sequence selected from the group consisting of SEQ ID NO: 5-8, 10, 12, 14, 16, 24, 27, 28, 34, 35, 37, 40, 42, 44-46, 79, 97, 100, 101, and 116, and combinations thereof.

Embodiments of the present invention are directed generally to antisense compounds and compositions for the treatment of muscular dystrophy, and in particular, Duchenne muscular dystrophy (DMD). In one embodiment, the invention is directed to antisense oligonucleotide molecules, pharmaceutical compositions and formulations comprising antisense oligonucleotide molecules, and methods of treating muscular dystrophy related diseases and disorders wherein the antisense oligonucleotide molecules comprises a base sequence selected from the group consisting of SEQ ID NO: 5-8, 10, 12, 14, 16, 24, 27, 28, 34, 35, 37, 40, 42, 44-46, 79, 97, 100, 101, and 116, and combinations thereof.

Methods for treating muscular wasting diseases such as Duchenne muscular dystrophy are disclosed. Specifically, the methods include administering to a subject in need of treatment for a muscular wasting disease, an NF-κB activation inhibitor capable of blocking the activation of NF-κB.

The invention relates to methods and materials for enhancing muscle mass or for the treatment of muscle disease in a subject, comprising introducing a cell which has a lower than normal level of myostatin signalling, into the subject.

Combinations comprising (or consisting essentially of) one or more compounds of formula (1) with one or more ancillary agents, to processes for preparing the combinations, and to various therapeutic uses of the combinations. Also provided are pharmaceutical compositions containing the combinations as well as a method of treatment of Duchenne muscular dystrophy, Becker muscular dystrophy or cachexia using the combinations.

The invention discloses a method for separately culturing a human adipose mesenchymal stem cell and a dedicated culture medium thereof. The culture medium used for separately culturing the human adipose mesenchymal stem cell comprises an animal cell basic culture medium, fetal calf serum, an epidermal growth factor and a platelet-derived growth factor. The final concentration of the fetal calf serum is 1-200 mL / L, the final concentration of the epidermal growth factor is 1-100 ng / ml, and the final concentration of the platelet-derived growth factor is 1-100 ng / ml. The adipose mesenchymal stem cell of the invention has CD31-, CD34-, CD45- and HLA-DR-, as well as the phenotype of CD29+, CD44+, CD105+ and Flk-1+. The specificity cell surface marker and the relevant antihelion molecule of a skeletal muscle cell and a vascular endothelia cell can be expressed after inducement is performed in vitro. Muscle fiber, vascular endothelin and functional muscle satellite cells can be differentiated in a muscle injury model mouse body caused by medicine and the expression of dystrophin protein on the ducheme muscular dystrophy (DMD) model mouse (mdx) myolemma can be partially recovered, so as to release the pathological symptom of the model mouse.

The present invention relates to a gene therapy method for the treatment of Duchenne muscular dystrophy, or DMD.

Provided herein are stem cell and exosome compositions having therapeutic utility to treat a variety of diseases and disorders, e.g., cardiovascular disease, Duchenne muscular dystrophy, and fibrotic disease.

The invention provides compositions and methods for treating, preventing, and diagnosing diseases or conditions associated with an abnormal level or activity of biglycan; disorders associated with an unstable cytoplasmic membrane, due, e.g., to an unstable dystrophin associated protein complex (DAPC); disorders associated with abnormal synapses or neuromuscular junctions, including those resulting from an abnormal MuSK activation or acetylcholine receptor (AChR) aggregation. Examples of diseases include muscular dystrophies, such as Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, neuromuscular disorders and neurological disorders.

This invention relates, e.g., to a method for enhancing exon skipping in a pre-mRNA of interest, comprising contacting the pre-mRNA with an effective amount of a compound such as, for example, Perphenazine, Flupentixol DiHCl, Zuclopenthixol or Corynanthine HCl, or a compound which shares a similar 2-D structure and activity level with one of these compounds, or a pharmaceutically acceptable salt, hydrate, solvate, or isomer of the compound, and, optionally, with an antisense oligonucleotide that is specific for a splicing sequence in the pre-mRNA Methods for treating Duchenne muscular dystrophy (DMD) are disclosed.

The invention provides compositions and methods for treating, preventing, and diagnosing diseases or conditions associated with an abnormal level or activity of biglycan; disorders associated with an unstable cytoplasmic membrane, due, e.g., to an unstable dystrophin associated protein complex (DAPC); disorders associated with abnormal synapses or neuromuscular junctions, including those resulting from an abnormal MuSK activation or acetylcholine receptor (AChR) aggregation. Example of diseases include muscular dystrophies, such as Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, neuromuscular disorders and neurological disorders.

The present invention relates to novel α-keto carbonyl calpain inhibitors for the treatment of neurodegenerative diseases and neuromuscular diseases including Duchenne Muscular Dystrophy, Becker Muscular Dystrophy and other muscular dystrophies. Disuse atrophy and general muscle wasting can also be treated. Diseases of the eye, in particular cataract, can be treated as well. Generally all conditions where elevated levels of calpains are involved can be treated. The compounds of the invention may also inhibit other thiol proteases such as cathepsin B, cathepsin H, cathepsin L, papain or the like. Multicatalytic Protease (MCP) also known as proteasome may also be inhibited and the compounds can therefore be used to treat cell proliferative diseases such as cancer, psoriasis, and restenosis. The compounds of the present invention are also inhibitors of cell damage by oxidative stress through free radicals and can be used to treat mitochondrial disorders and neurodegenerative diseases, where elevated levels of oxidative stress are involved.

This invention provides substituted acylanilide compounds and uses thereof in treating a variety of diseases or conditions in a subject, including, inter alia, a muscle wasting disease and / or disorder such as muscular dystrophies including Duchenne muscular dystrophy and Becker muscular dystrophy.

This invention is directed to substituted acylanilide compounds and uses thereof in treating a variety of diseases or conditions in a subject, including, inter alia, a muscle wasting disease and / or disorder such as Duchenne muscular dystrophy or Becker muscular dystrophy.

The mdx mouse is a model of Duchenne muscular dystrophy. The present invention describes that mdx mice exhibited clinically relevant cardiac phenotypes. A non-invasive method of recording electrocardiograms (ECGs) was used to a study mdx mice (n=15) and control mice (n=15). The mdx mice had significant tachycardia, consistent with observations in patients with muscular dystrophy. Heart-rate was nearly 15% faster in mdx mice than control mice (P<0.01). ECGs revealed significant shortening of the rate-corrected QT interval duration (QTc) in mdx mice compared to control mice (P<0.05). PR interval duration were shorter at baseline in mdx compared to control mice (P<0.05). The muscarinic antagonist atropine significantly increased heart-rate and decreased PR interval duration in C57 mice. Paradoxically, atropine significantly decreased heart-rate and increased PR interval duration in all mdx mice. Pharmacological autonomic blockade and baroreflex sensitivity testing demonstrated an imbalance in autonomic nervous system modulation of heart-rate, with decreased parasympathetic activity and increased sympathetic activity in mdx mice. These electrocardiographic findings in dystrophin-deficient mice provide new bases for diagnosing, understanding, and treating patients with Duchenne muscular dystrophy.

The invention relates to methods of treating Duchenne muscular dystrophy with flavonoids. The methods may include (a) providing a pharmaceutical composition comprising a therapeutically effective amount of flavonoid, and (b) administering the composition to a human patient, wherein the flavonoid comprises an isoflav-4-one with at least one of the carbons located at positions 8, 7, 6, 5, 2, 2′, 3′, 4′, 5′, or 6′ modified by an alcohol group. Alternatively, the flavonoid may comprise (1) a flavan-3-ol with at least one of the carbons located at positions 8, 7, 6, 5, 4, 2′, 3′, 4′, 5′, or 6′ modified by an alcohol group, or (2) a Free-B-Ring flavone with at least one of the carbons located at positions 8, 7, 6, 5 or 3 modified by an alcohol group and with at least one of the carbons located at positions 8, 7, 6, 5 or 3 modified by a glycoside group.

Combinations comprising (or consisting essentially of) one or more compounds of the formula (I) or (II) with one or more ancillary compounds, to processes for preparing the combinations, and to various therapeutic uses of the combinations. Also provided are pharmaceutical compositions containing the combinations as well as a method of treatment of Duchenne muscular dystrophy, Becker muscular dystrophy or cachexia using the combinations.

The invention relates to methods of treating Duchenne muscular dystrophy with flavonoids. The methods may include (a) providing a pharmaceutical composition comprising a therapeutically effective amount of flavonoid, and (b) administering the composition to a human patient, wherein the flavonoid comprises an isoflav-4-one with at least one of the carbons located at positions 8, 7, 6, 5, 2, 2′, 3′, 4′, 5′, or 6′ modified by an alcohol group. Alternatively, the flavonoid may comprise (1) a flavan-3-ol with at least one of the carbons located at positions 8, 7, 6, 5, 4, 2′, 3′, 4′, 5′, or 6′ modified by an alcohol group, or (2) a Free-B-Ring flavone with at least one of the carbons located at positions 8, 7, 6, 5 or 3 modified by an alcohol group and with at least one of the carbons located at positions 8, 7, 6, 5 or 3 modified by a glycoside group.

A microutrophin containing a utrophin having internal deletions (relative to a native utrophin) in the hinge regions and a C-terminal deletion is provided. Also provided are vectors and compositions useful for delivering the microutrophin for the treatment of muscular disorders, including Duchenne Muscular Dystrophy.

The present disclosure relates to an inhibitor of Dynamin 2 or composition comprising the same for use in the treatment of Duchenne's muscular dystrophy.