39 results about "Muscular spinal atrophy" patented technology

The present invention concerns the development of a quantitative method for the molecular diagnosis of autosomal recessive spinal muscular atrophy (SMA) by measuring the amount of cytosolic mRNA from human muscle cells. Both the procedure using radioactive material and the Enzyme-Linked Immunosorbent Assay (ELISA) nonradioactive method were developed using 32P-dCTP labeled and biotinylated nucleotide probes. The results obtained demonstrate that the measurement of mRNA could be used as a quantitative method for the molecular diagnosis of SMA. There was a perfect concordance of the results obtained between the procedure using radioactive material, the ELISA method and the single strand conformation polymorphism (SSCP) analysis regarding the negative and positive SMA samples. The methods developed in this study may be applicable to the diagnosis (detection of homozygous and heterozygous deletions in exons 7 and 8 of the SMN gene) and the control of mRNA concentrations in the future gene therapy of patients with SMA.

The invention relates to a method for detecting a genetic disease gene and particularly discloses a method for detecting a spinal muscular atrophy virulence gene. The method comprises the following steps: 1, performing enrichment processing on SMN1 and SMN2; 2, preparing a nanopore sequencing library for sequencing; 3, sequencing by a sequenator; and 4, performing clinical report evaluation on the obtained sequence file. The method is convenient to use, low in cost and can effectively and accurately detect the copy number of the spinal muscular atrophy virulence gene, the small segment insertion and deletion, the point mutation, the noncoding region mutation and even the gene translocation, and brings help and breakthrough for the clinical diagnosis and scientific research on the spinal muscular atrophy.

It has been discovered that pharmacological inhibition of K+ channels (using the FDA-approved broad-spectrum K+ channel antagonist 4-AP) positively benefitted smn mutant phenotypes, a result that is consistent with the defective excitability of motor circuits by their interneuron or sensory neuron inputs being a critical consequence of SMN depletion. Based on these observations, certain embodiments of the invention are directed to methods of treatment of SMA by administering therapeutically effective amounts of one or more potassium channel antagonists, including 4-aminopyridine, 4-(dimethylamino)pyridine, 4-(methylamino)pyridine, and 4-(aminomethyl)pyridine. Other embodiments are directed to new pharmaceutical formulations comprising two or more potassium channel antagonists.

Provided herein are methods and associated compositions, kits, systems, devices and instruments useful for genetic analysis where there i s/a re a sequence(s) similar to the gene of interest in a sample, e.g. for determining the spinal muscular atrophy (SMA) carrier status. In the methods, a combined copy number for related genes (e.g., a gene of interest and its pseudogene, e.g. SMN1 and SMN2) can be determined via an assay. In addition, relative amounts of the related genes, i.e., a ratio of the related genes can be determined via the assay. Using the data of the combined copy number and the ratio of the related genes, the genotype of the gene of interest (as well as its pseudogene(s), if desired) can be determined with high accuracy.

The present invention relates to a recombinant adeno-associated virus (rAAV) vector comprising a serotype 9 or rh10 AAV capsid, for use in a method for the treatment of spinal muscular atrophy (SMA).

The invention relates to a method of knocking out spinal muscular atrophy SMN genes and a cell model. The cell model is constructed by adopting the following steps: (1) constructing and designing zinc finger nuclease plasmids for knocking out the SMN genes; (2) transferring the constructed ZFN plasmids for knocking out the SMN genes into mammalian cells by using a lipidosome method; (3) detecting the effectiveness of the ZFN gene knockout by using a genome PCR product of a ZFN peculiar knockout site and DNA sequence determination; (4) specific to the cells, the ZFN genes of which are effectively knocked out, carrying out monoclonal separation and identifying cell knockout types one by one; (5) carrying out mRNA level identification on gene knockout cell strains; (6) carrying out protein expression level identification on the gene knockout cell strains. The spinal muscular atrophy pathology cell model can be used for research of SMA pathogenesis; medicines can be screened by detecting the level of protein expression of SMN compounds in the cell model.

The invention discloses a primer group and a kit for detecting copy number and point mutation of a single-tube human spinal muscular atrophy related gene and typing a carrier. The nucleotide sequencesof the primer group are shown as SEQ ID NO. 1 to 38. The primer group is reasonable in design and high in specificity. The amplification bias is reduced, and the quantification accuracy is ensured. An identification sequence is introduced to realize identification of the conversion condition of the seventh exon of the SMN1 and the SMN2. UDG enzyme is introduced, and amplification products are cut, so as to avoid pollution. Clinical applications such as SMN1/2 gene copy number detection of human amyotrophy, SNP site detection of SMN1/2 Chinese population, NAIP and GTF2H2 gene copy number detection, typing of patients (I- VI types) and carriers ('1 + 0' and '2 + 0') and the like are simultaneously realized by the single tube. The method and the kit are rapid in detection, accurate in result, appropriate in cost, high in clinical occupancy of applicable instruments and suitable for clinical application.

The invention provides a digital PCR kit for detecting spinal muscular atrophy. The digital PCR kit is a digital PCR kit for simultaneously detecting an SMN1 exon 7, an SMN1 exon 8, an SMN2 exon 7 andan internal reference gene in a sample to be detected in a one-tube digital PCR reaction, and the SMN1 exon 7, the SMN1 exon 8, the SMN2 exon 7 and the internal reference gene are simultaneously detected in at least four fluorescence channels. The kit disclosed by the invention is based on a digital PCR technology, can be used for quantitatively detecting the copy numbers of the SMN1 exons 7 and8 and the SMN2 in one tube, and can be applied to SMA clinical definite diagnosis, carrier screening and disease typing.

A rAAV vector is described herein which has an AAVhu68 capsid and at least one expression cassette in the capsid. The at least one expression cassette comprises nucleic acid sequences encoding a functional SMN protein and expression control sequences that direct expression of the SMN sequences in a host cell. Also provided are compositions containing this rAAVhu68.SMN vector and methods of using same for spinal muscular atrophy in a patient.

Disclosed herein are compositions comprising AAV9 viral vectors and methods of using them to treat SMA patients, e.g., Type II and Type III Spinal Muscular Atrophy (SMA) patients.

The invention discloses a primer-probe combination for simultaneously screening spinal muscular atrophy and primary immunodeficiency diseases, application of the primer-probe combination, a detectionkit and a detection method. The detection kit comprises primers and probes for screening and detecting a spinal muscular atrophy gene and primers and probes for screening and detecting genes (TREC andKREC) of the primary immunodeficiency diseases (advanced-case combined immunodeficiency disease and agammaglobulinemia). According to the primer-probe combination, the application of the primer-probecombination, the detection kit and the detection method, a multiple digital PCR detection system with high sensitivity, high accuracy, low cost and short cycle can be established, quantified detection on a copy number of a pathogenic gene of a hereditary disease, i.e., the spinal muscular atrophy (SMA), a copy number of an advanced-case combined immunodeficiency disease related marker TREC and acopy number of an agammaglobulinemia related marker KREC can be achieved simultaneously in one reaction, and thus, the above-mentioned three kinds of diseases are screened in one time.

Disclosed are 20-hydroxyecdysone and the derivatives thereof, intended for use in the treatment of a neuromuscular disease such as spinal muscular atrophy or amyotrophic lateral sclerosis, or more particularly in the treatment of a specific disorder of the motor neurons causing alterations in the muscular function occurring in the context of these neuromuscular diseases.

The invention provides an SMN2 gene copy number variation detection kit, and particularly develops a method, a primer, a probe and a kit for rapidly and qualitatively detecting deletion of a seventh exon of a human spinal muscular atrophy (SMA) key pathogenic gene and a motor neuron survival gene SMN2 based on a digital PCR (Polymerase Chain Reaction) platform, and a kit for rapidly and qualitatively detecting deletion of a seventh exon of a human spinal muscular atrophy (SMA) key pathogenic gene and deletion of a seventh exon of a motor neuron survival gene SMN2. Experimental results show that the detection system provided by the invention has extremely high sensitivity and accuracy.

This prophylactic or therapeutic agent for spinal muscular atrophy includes a compound represented by formula (I) or a salt thereof (in the formula: W1, W2, and W3 are each independently selected fromthe group consisting of C-R2, C-R3, C-Rc, and C-Rd, and are defined as in any of (i) to (iv); (i) when W3 is C-R2, W1 is C-R3, W2 is C-Rc or N, and R1 is a hydrogen atom; (ii) when W3 is C-R3, W1 isC-R2, W2 is C-Rc or N, and R1 is a hydrogen atom, a C1-8 alkyl, or a C1-8 alkoxy; (iii) when W1 is C-R2, W2 is C-Rc or N, W3 is C-Rd, and R1 is an aliphatic heterocycle that contains at least one nitrogen atom and is optionally substituted with a non-aromatic substituent; (iv) when W2 is C-R2, W1 is C-Rc, W3 is C-Rd, and R1 is an aliphatic heterocycle that contains at least one nitrogen atom and is optionally substituted with a non-aromatic substituent; R2 is an aromatic ring of at least six members that is optionally substituted with a non-aromatic substituent; R3 is an aliphatic heterocyclethat contains at least one nitrogen atom and is optionally substituted with a non-aromatic substituent; Q1 is selected from C-Ra and N; Q2 is selected from C-Rb and N; and Ra, Rb, Rc, and Rd are eachindependently selected from the group consisting of a hydrogen atom, halogen, a C1-8 alkyl, a C1-8 alkoxy, and a cyano group).