Methods and materials are described for human genome prophylaxis and therapy of diseases using myoblast transfer. These methods result in gene transcript changes in multiple pathways. Linking the myoblast transfer technology development from DMD, cardiomyopathy, and Type-II diabetes, the myoblast transfer demonstrably mediates its effect through transfer of the normal myoblast nuclei that supply the complete human genome, in addition to just replenishing the missing gene(s) or the aberrant gene(s). The replacement genes then transcribe to produce the necessary proteins or factors for genetic repair. A variety of uses of this technology are described, including that for disease treatment, disease prevention, drug discovery, and selection of superior cells and clones for therapy

The present invention relates to a amyotrophic lateral sclerosis (ALS) diagnostic composition using acid sphingomyelinase (ASM), and a method for detecting diagnostic markers and, more specifically, to a method and a composition for detecting markers for ALS, the method comprising the steps of: (a) providing a sample of a subject; (b) measuring the ASM expression level or the enzyme activation level in the sample; (c) determining that a subject, of which the ASM expression level or the enzyme activation level is increased compared to that of a normal person, has ALS. According to the investigation of the present inventors, the activity of ASM, among lipids and enzymes related to the sphingolipid metabolism, is specifically increased in a sample of an ALS patient compared to that of a normal person. ASM can be used as a marker for diagnosing ALS, thereby enabling the development of a novel and effective diagnostic reagent.

The present invention is in the field of transactive response DNA binding protein with a molecular weight of 43 kDa (TARDB or also TDP-43). The invention relates to TDP-43 specific binding molecules, in particular to anti-TDP-43 antibodies or an antigen-binding fragment or a derivative thereof and uses thereof. The present invention provides means and methods to diagnose, prevent, alleviate and/or treat a disease, disorder and/or abnormality associated with TDP-43 aggregates including but not limited to Frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Chronic Traumatic Encelopathy (CTE), and limbic-predominant age-related TDP-43 encephalopathy (LATE).

Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy. Also provided are kits for detecting the amount of SMN protein in a sample of cerebrospinal fluid.

The present invention relates to uses and methods comprising one or more RANK/RANKL antagonists or of a pharmaceutical composition comprising one or more RANK/RANKL antagonists and a pharmaceutically acceptable carrier for treating neuromuscular disorders, non-genetic myopathies, or genetic myopathies; maintaining and/or preserving the excitation:contraction:relaxation coupling; reducing loss of muscle strength associated with neuromuscular disorders, non-genetic myopathies or genetic myopathies; reducing the loss of muscular strength associated with skeletal or cardiac muscle disuse, diseases and aging; or regulating skeletal or cardiac muscle disuse, diseases and/or aging in a patient in need thereof. The present invention also relates to combinations and compositions comprising one or more RANK/RANKL antagonists and to methods for identifying candidate compounds.

Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy. Also provided are kits for detecting the amount of SMN protein in a sample of cerebrospinal fluid.

Aspects of the disclosure relate to methods of altering RNA splicing in a subject. In some embodiments, methods are provided for correcting splicing in a cell that contains a DYSF gene having a mutation that results in defective splicing.

Provided are methods of determining an amount of alpha-dystroglycan (αDG) in a sample, determining an amount of the glycosylated form of αDG in the sample, and determining a ratio of the amount of the glycosylated form of αDG to the amount of αDG in the sample.

Disclosed is a method for acquiring information on spinal muscular atrophy, comprising acquiring a fluorescence image of a nucleated cell in a measurement sample, wherein the measurement sample is a sample prepared from a blood specimen obtained from a subject, an SMN protein in the nucleated cell is labeled with a first fluorescent dye, and a predetermined nuclear protein in the nucleated cell is labeled with a second fluorescent dye, acquiring an intracellular distance between a first bright spot corresponding to the first fluorescent dye and a second bright spot corresponding to the second fluorescent dye in the fluorescence image, and acquiring a value regarding a number of nucleated cells in which the intracellular distance is equal to or less than a first threshold value, wherein the value is an indicator of spinal muscular atrophy affection.

A method is provided which makes it possible to analyze an SMN protein nuclear body that serves as a more highly reliable biomarker. The present method is for analyzing the expression of an SMN protein nuclear body, comprising: labeling one or more surface antigen markers of blood-derived nucleated cells in a sample containing the nucleated cells with one or more label antibodies; labeling SMN protein in the nucleated cells; labeling nuclei of the nucleated cells; selecting one cell population from a plurality of cell populations in which nuclei and SMN protein in the nucleated cells have been labeled and which have been classified based on, e.g., surface antigen markers labeled with label antibodies; and analyzing the expression of an SMN protein nuclear body of the selected cell population based on a label on SMN protein. The method comprises performing imaging flow cytometry using an objective lens with a predetermined magnification.