Abstract: Disclosed are pharmaceutical compositions and methods for treating or preventing muscle diseases or the symptoms thereof. The compositions typically include and the methods typically utilize phosphodiesterase type 5A inhibitors.

Abstract: Disclosed are pharmaceutical compositions and methods for treating or preventing muscle diseases or the symptoms thereof. The compositions typically include and the methods typically utilize phosphodiesterase type 5A inhibitors.

Abstract: Disclosed are pharmaceutical compositions and methods for treating or preventing muscle diseases or the symptoms thereof. The compositions typically include and the methods typically utilize phosphodiesterase type 5A inhibitors.

Abstract: Disclosed are pharmaceutical compositions and methods for treating or preventing muscle diseases or the symptoms thereof. The compositions typically include and the methods typically utilize phosphodiesterase type 5A inhibitors.

Abstract: Disclosed is a method for the prevention and/or treatment of muscle degeneration. In this method, a subject recognized as having muscle degeneration is treated with a composition effective to increase functional glycosylation of ?-dystroglycan in an affected tissue in the subject. Functional glycosylation is to be increased to an extent wherein the binding of ?-dystroglycan to its ligands in the affected tissue is rescued to levels substantially similar to those in an evenly matched tissue unaffected by degeneration. One effective means for increasing functional glycosylation of ?-dystroglycan in a subject includes increasing glycosyltransferase activity, such as LARGE or LARGE2 activity, in the muscle of the subject. Therapeutic glycosylated peptide compositions are also provided.

Abstract: Disclosed is alpha-dystroglycan protein (alpha-DG) in glycosylated and functional form. The disclosed alpha-DG binds to the basal lamina and to the sarcolemma of muscle fibers and may be injected into muscle and incorporated into muscle fibers in order to restore membrane integrity where the muscle fibers comprise a dysfunctional alpha-DG protein. Alpha-DG as disclosed herein may be utilized in pharmaceutical compositions and methods for treating diseases and disorders associated with or characterized by a dysfunctional alpha-DG, such as muscular dystrophy.

Abstract: Disclosed are pharmaceutical compositions and methods for treating or preventing muscle diseases or the symptoms thereof. The compositions typically include and the methods typically utilize phosphodiesterase type 5A inhibitors.

Abstract: Disclosed is a method for diagnosing the tumorigenic grade of a malignant tissue. The method entails determining the amount of dystroglycan protein of the malignant tissue relative to a standard. Suitable methods for determining the amount of dystroglycan protein of the tissue are provided, and include measuring the amount of mRNA transcripts which encode dystroglycan, and also performing western blot analysis or immunofluorescence analysis on the tissue components to detect &agr;-dystroglycan or &bgr;-dystroglycan. An antibody probe which binds specifically to the C-terminus of &bgr;-dystroglycan, is provided. This method is applicable to human malignant tissue, especially adenocarcinoma, and preferably prostate or mammary adenocarcinoma. This method can also be applied to the detection of a cancerous disease state in a tissue of a patient, with a decreased level of dystroglycan protein being indicative of the presence of cancer.

Abstract: Disclosed are mammalian nucleic acid sequences encoding a neuronal-specific subunit of a voltage-gated calcium channel. Specifically disclosed are &ggr;2, &ggr;3 and &ggr;4 subunits. In other aspects, the disclosure relates to expression vectors which encode neuronal-specific subunits, as well as cells containing such vectors. In other aspects, the disclosure relates to antigenic fusion proteins comprising at least a portion of a mammalian neuronal-specific subunit of a voltage-gated calcium channel. Such fusion proteins are useful, for example, in the production of antibodies specifically reactive with the subunits of the invention. The nucleic acid sequences of the invention find application, for example, in screening for compounds which modulate the activity of neuronal voltage-gated calcium channels and also in diagnostic methods for diagnosing the autoimmune disease Lambert-Eaton Syndrome, as well as diagnosing defects in &ggr; subunit genes of a patient with a neuronal disease such as epilepsy.

Abstract: The present invention relates to the discovery that the &agr;-dystroglycan receptor is required for Mycobacterium leprae entry into cells, assays for high throughput screening of drugs for use in treatments against leprosy, and methods for studying the role of the receptor in neurodegenerative and musculodegenerative diseases, and the like.

Abstract: Disclosed within is a mouse, and cells derived therefrom, which are homozygous for a disrupted &dgr;-sarcoglycan gene, the disruption in said gene having been introduced into the mouse or an ancestor of the mouse at an embryonic stage. Said disruption prevents the synthesis of functional &dgr;-sarcoglycan in cells of the mouse and results in the mouse having a reduced amount of &bgr;- and &egr;-sarcoglycan and sarcospan, and a disruption of the sarcoglycan-sarcospan complex in smooth muscle of the mouse. Said disruption also results in a reduced amount of sarcospan, &agr;-, &bgr;-, &ggr;-, and &egr;-sarcoglycan in the sarcolemma of skeletal and cardiac muscles of the mouse, compared to the amounts of said components in a mouse lacking disrupted &dgr;-sarcoglycan genes. Preferred specific disruptions of the &dgr;-sarcoglycan gene are listed.

Abstract: Disclosed is a method for treating a patient suffering from the disease sarcoglycan-deficient limb-girdle muscular dystrophy by gene replacement therapy. Sarcoglycan gene replacement therapy produces extensive long-term expression of the sarcoglycan species which restores the entire sarcoglycan complex, results in the stable association of alph&agr;-dystroglycan with the sarcolemma, and eliminates the morphological markers of limb-girdle muscular dystrophy. In another aspect, the invention relates to a method for determining a specific defective sarcoglycan species in the tissue of a patient. The method involves culture of muscle cells obtained from the patient, and the independent introduction of expression vectors encoding each of the sarcoglycan species, &agr;, &bgr;, &ggr;, and &dgr;, into the cultured cells with subsequent assaying for restoration of the dystrophin-glycoprotein complex.

Abstract: Disclosed herein is a substantially pure nucleic acid sequence encoding a mammalian 35 kDa non-dystrophin component (&dgr;-sarcoglycan) of the dystrophin-glycoprotein complex. Also disclosed are the amino acid sequence and an immunogenic peptide of &dgr;-sarcoglycan. The peptide when used to immunize a mammal, stimulates the production of antibodies which bind specifically to the &dgr;-sarcoglycan. Methods to identify mutations in the &dgr;-sarcoglycan gene associated with autosomal recessive limb-girdle muscular dystrophy are also disclosed. The identification of such mutations enables the design of nucleic acid probes which hybridize specifically to a mutant form of &dgr;-sarcoglycan, or the complement thereof, but not to the DNA of the wild-type form of the gene (or the complement thereof), under stringent hybridization conditions. Such probes are useful, for example, in connection with the diagnosis of autosomal recessive limb-girdle muscular dystrophy.

Abstract: Disclosed is a transgenic knockout mouse whose genome has a homozygous disruption in its endogenous sarcospan gene, wherein the disruption prevents the synthesis of functional sarcospan in cells of the mouse. The mouse is characterized as exhibiting from 1.4 to 6.8 fold larger epididymal fat pad deposits as compared to the epididymal fat pad deposits of a wild type mouse. Methods for production of the mouse are presented. Also disclosed are cells derived from the transgenic knockout mouse. The mouse can be used in a method for identifying therapeutic agents for the treatment of an individual diagnosed with a metabolic disorder associated with a reduction or loss of expression of wild-type sarcospan. An example of such a disorder is weight gain in the individual associated with a reduction or loss of expression of wild-type sarcospan. These specific methods are also provided.

Abstract: Disclosed is a mouse, cells derived therefrom, and methods for using the mouse, the mouse being homozygous for a disrupted &dgr;-sarcoglycan gene, the disruption in the gene having been introduced into the mouse or an ancestor of the mouse at an embryonic stage. The disruption prevents the synthesis of functional &dgr;-sarcoglycan in cells of the mouse and results in the mouse having a reduced amount of &bgr;- and &egr;-sarcoglycan and sarcospan, and a disruption of the sarcoglycan-sarcospan complex in smooth muscle of the mouse. Also disclosed is a mouse, cells derived therefrom, and methods for using the mouse, the mouse being homozygous for a disrupted &bgr;-sarcoglycan gene, the disruption in the gene having been introduced into the mouse or an ancestor of the mouse at an embryonic stage.

Abstract: Disclosed are compositions and methods for aiding in the diagnosis of congenital muscular dystrophy associated with in-frame deletion in the laminin-2 .alpha.2 polypeptide chain in an individual. In a preferred diagnostic method embodiment, an experimental muscle tissue sample is provided from the individual and treated if necessary to render components available for antibody binding. The components of the sample are then separated on the basis of molecular weight. The separated protein components are then transferred to a solid support while maintaining the relative positions established in separation step. The transferred components are then stained with an affinity reagent which is known to bind to a C-terminal domain of the laminin-2 .alpha.2 polypeptide chain. Individual afflicted with congenital muscular dystrophy associated with in-frame deletion in the laminin-2 .alpha.2 polypeptide chain on the basis of positive staining in combination with reduced molecular weight of the laminin-2 .alpha.

Abstract: Disclosed is a method for inhibiting the binding of an arenavirus to a cellular receptor. The method involves providing, in soluble form, a reagent comprising .alpha.-dystroglycan or a portion thereof, the reagent being characterized by the ability to bind to the arenavirus thereby inhibiting the binding of the arenavirus to the cellular receptor. The reagent is contacted with an arenavirus particle prior to infection of a cell by the arenavirus particle. Also disclosed are methods for treating an arenavirus infection in a patient and preventing an arenavirus infection in an individual at risk. These methods involve providing a therapeutic composition comprising .alpha.-dystroglycan or a portion thereof which is characterized by the ability to bind to arenaviruses, thereby inhibiting the binding of arenaviruses to a cellular receptor; and administering the composition to the patient or individual at risk.

Abstract: Disclosed is a method for aiding in the diagnosis of merosin deficiency-type congenital muscular dystrophy (CMD). The method is based on the discovery of a previously unidentified form of CMD which is characterized by a substantial reduction in the levels of merosin in skeletal muscle tissue containing normal levels of dystrophin and dystrophin-associated proteins.

Abstract: Disclosed herein is a substantially pure nucleic acid sequence encoding a mammalian 35 kDa non-dystrophin component (.delta.-sarcoglycan) of the dystrophin-glycoprotein complex. Also disclosed are the amino acid sequence and an immunogenic peptide of .delta.-sarcoglycan. The peptide when used to immunize a mammal, stimulates the production of antibodies which bind specifically to the .delta.-sarcoglycan. Methods to identify mutations in the .delta.-sarcoglycan gene associated with autosomal recessive limb-girdle muscular dystrophy are also disclosed. The identification of such mutations enables the design of nucleic acid probes which hybridize specifically to a mutant form of .delta.-sarcoglycan, or the complement thereof, but not to the DNA of the wild-type form of the gene (or the complement thereof), under stringent hybridization conditions. Such probes are useful, for example, in connection with the diagnosis of autosomal recessive limb-girdle muscular dystrophy.

Abstract: Disclosed herein are compositions and methods for the detection of primary adhalinopathy. More specifically, disclosed herein are nucleic acid probes which hybridize specifically, under stringent hybridization conditions, to a mutant adhalin gene or the complement thereof, but not to the corresponding region of a wild-type adhalin gene. Also disclosed are methods for the detection of a mutation in the human adhalin gene which is responsible for primary adhalinopathy. Such methods include the use of the nucleic acid probes of the invention for detection of the myopathy by hybridization, as well as detection by direct DNA sequencing techniques.