52 results about "Spinal muscular atrophies" patented technology

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.

Methods for using tetracycline compounds for the treatment of spinal muscular atrophy are described.

The present provides methods for treating spinal muscular atrophy using a self-complementary recombinant adeno-associated virus (rAAV) viral particle comprising a transgene expressing SMN. In one aspect, the viral particles are administered the spinal column or cisterna magna in a human subject; for example, a pediatric human subject. Viral particles comprising AAV9 capsids are contemplated.

Disclosed are methods for treating neurodegenerative diseases such as Amyotrophic Lateral Sclerosis, Alzheimer's Disease, Parkinson's Disease, Myasthenia Gravis, Multifocal Motor Neuropathy, Primary Lateral Sclerosis, Spinal Muscular Atrophy, Kennedy's Disease, and Spinocerebellar Ataxia, by administration of a compound that blocks the interaction of CD40 and CD40L.

This invention provides methods for the treatment, prevention, and/or amelioration of symptoms relating to lower motor neuron diseases (such as spinal muscular atrophy). The methods comprise administration of an agonist anti-trkC antibody. Compositions and kits are also provided.

The invention relates to a method for the treatment of spinal muscular atrophy comprising administering a therapeutically effective amount of a therapeutically acceptable salt of phenylbutyrate to a subject in need of treatment of spinal muscular atrophy.

A highly concentrated preparation of sodium 4-phenylbutyrate in an aqueous medium as an alternative for present high dosage therapeutic treatments of certain disorders is provided, specifically for the treatment of spinal muscular atrophy (SMA), central nervous system (CNS) cancer, myelodysplastic syndrome (MS), acute leukemia, glioblastoma multiforme, amyotrophic lateral sclerosis (ALS), and colon cancer.

The invention discloses a detection kit and a method for copy number of spinal muscular atrophy pathogenic gene SMN1 based on a real-time fluorescence quantitative PCR (Polymerase Chain Reaction) technique. The detection kit comprises specific primers SMN1-F (SEQ ID NO.1) and SMN1-R (SEQ ID NO.2) modified by NO.7 exon locked nucleic acid of a pair of target genes SMN1, an SMN1 detection probe (SEQID NO.3), an SMN2 gene closed probe SMN2-B (SEQ ID NO.4) modified by SMN-P locked nucleic acid and 3'end C3Spacer, gene primers ALB-F (SEQ ID NO.5) and ALB-R (SEQ ID NO.6) of a reference gene ALB andan ALB detection probe ALB-P (SEQ ID NO.7). The amplification specificity and amplification efficiency of the SMN1 gene are enhanced by using locked nucleic acid modification; a stable reaction system for double amplification of the target genes and the reference gene is established by using a multi-PCR principle and optimizing reaction systems and conditions, and further quantitative accuracy and reliability of the copy number of the SMN1 can be ensured; good repeatability and high operability are obtained.

The present invention provides compounds of formula (I) wherein A, B, X, Y, R1 and R2 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments.

The invention relates to a detection method and a kit for spinal muscular atrophy related gene mutation. The detection method comprises the following steps: extracting whole genome DNA of an object; carrying out PCR amplification on the obtained whole genome DNA by virtue of a PCR primer pair I, a PCR primer pair II, a PCR primer pair IIII and a PCR primer pair IV, so as to obtain a PCR amplification product; analyzing the obtained PCR amplification product, and judging whether four sites of spinal muscular atrophy related genes in the whole genome DNA of a to-be-detected sample. The kit comprises the PCR primer pair I, the PCR primer pair II, the PCR primer pair IIII and the PCR primer pair IV. The detection method and the kit have the beneficial effects that the design is smart, the sample is saved, meanwhile, three genes can be detected, the detection is rapid, accurate, simple and convenient, and a detection result can be taken as a reference basis of diagnosis, treatment and medication of physicians; the detection method and the kit are applicable to large-scale popularization and application.

The invention relates to a gene detection probe, a primer and a kit for spinal muscular atrophy, wherein the gene detection probe for spinal muscular atrophy comprises a probe SMN1-7 for detecting a SMN1 gene, and the nucleotide sequence is shown in SEQ ID No. 1; a probe SMN2-7 for detecting a SMN2 gene, and the nucleotide sequence is shown in SEQ ID No. 2. According to the invention, a multiple fluorescence quantitative detection system with high specificity and low cost is established. High frequency pathogenic mutation detection of the SMN1 and SMN2 genes in one tube is realized. In addition, a multiple scorpion tail primer amplification system is established, so that the problem of the amplification consistency of the multiple fluorescence quantitative systems is solved, and the quantitative accuracy is improved.

The disclosure concerns methods and compositions for obtaining reliable copy numbers of highly homologous gene(s) using next generation sequencing. The methods determine whether or not an individual is a carrier of an autosomal recessive gene mutation using a determination of copy number of two genes, in specific embodiments. In at least some cases, an individual is identified whether or not he or she is a carrier or affected for a genetic defect in SMN1, wherein the defect is associated with spinal muscular atrophy.

The present invention relates to compounds useful as promoters of the SMN2 gene. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of Spinal Muscular Atrophy.

The invention discloses primers for detecting homozygous deletion mutation of spinal muscular atrophy related virulence genes SMN1 and SMN2. The primers comprise primers c.835-44, c.840, INS7+100, INS7+215 and *239 sites which amplify SMN1 and SMN2. By adopting a Sanger sequencing technology, the method can be used for detecting mutation conditions of c.835-44, c.840, INS7+100, INS7+215 and *239 sites in a body of the spinal muscular atrophy patient. The detection result finished by the invention is accurate and has important reference meaning in early screening of spinal muscular atrophy.

2,4-Diaminoquinazolines of formulae I-IV and VI

are useful for treating spinal muscular atrophy (SMA).

The present invention provides a method for increasing expression of survival motor neuron (SMN) protein based on a gene editing technology, and an application of the method in spinal muscular atrophy(SMA) treatment. The method for increasing the expression of the SMN protein is achieved by using a CRISPR/Cas9 technology to destroy splicing silencer ISS-N1 or ISS+100 on intron 7 of SMN2. The provided method for increasing the expression of the SMN protein is modified from a DNA level, and effective, safe, efficient, economical and practical. At the same time, the present invention also provides a series of applications of new methods for increasing the SMN protein in the SMA treatment, including specific sgRNA sequences for gene editing, gene editing reagents, gene editing plasmids, geneediting cells and preparation methods thereof, gene editing animal preparation methods and gene editing medicines.

The present invention provides compounds of formula (I)

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.