100 results about "Fragile X chromosome" patented technology

Compositions, kits and methods are provided for treating or preventing neurological disorders associated with aberrant silencing of gene expression by reestablishing the gene expression through inhibition of DNA methylation and / or histone deacetylase. The compositions and methods include administering to a patient suffering from the neurological disorder a therapeutically effective amount of a DNA methylation inhibitor, such as decitabine, preferably in combination with an effective amount of a histone deacetylase inhibitor. The compositions, kits and methods can be used to treat or present neurological disorders such as Lou Gehrig's disease, fragile X syndrome, Parkinson's disease and Alzheimer's disease.

The invention discloses a method for establishing a fragile X-syndrome non-human primate model on the basis of a CRISPR gene knockout technology. The method comprises the following steps: (1) establishing a FMR1 gene knockout machin model; (2) carrying out identification and related functional analysis on the machin model; (3) carrying out tests on the nerve characteristics and learning and memorizing ability of the machin model. The method utilizes a CRISPR gene knockout technology to establish a fragile X-syndrome non-human primate model. The model fills the blank of non-human primate model, can effectively stimulate the pathological process of human diseases, can be used as an optimum animal model for researching human diseases, can effectively predict the effect of novel vaccine, novel drug or novel diagnostic reagent in clinical applications, and thus greatly reduces the risk of novel drug development.

This invention provides methods of preserving, improving, or restoring cognitive function in mammal having one or more mutations in the FMR1 gene (e.g. at risk for or having fragile x syndrome), where the methods involve the brain derived neurotrophic factor (BDNF) level or activity in the brain of said mammal. In certain embodiments the methods involve administering one or more AMPA potentiators (e.g., ampakines) to the mammal in an amount sufficient to increase BDNF levels in the brain of the mammal.

The present invention provides methods of determining the size of a particular nucleic acid segment of interest in a sample of nucleic acids through fragmentation of DNA, size fractionation, an optional second fragmentation, and identification using a marker sequence. In particular aspects, an expansion or reduction of tandem repeat sequences can be detected. In further aspects, carriers and individuals afflicted with fragile X syndrome or other diseases associated with tandem repeats can be distinguished from normal individuals.

Methods for detecting a short tandem repeat polymorphism (STRP), such as fragile X syndrome, wherein PCR is used to amplify nucleic acid along the chromosome in the genomic DNA which includes all of the STRs of interest plus a substantial contiguous segment of the nucleic acid adjacent to the STRs. Single-stranded product is then obtained, and colorimetric-labeled oligonucleotides which target for (i) STRs and (ii) the contiguous DNA segment are hybridized with this single-stranded product which is then bound to a solid phase and separated from the remainder of the target material. The labeled oligonucleotide target material is recovered by treatment with base and then hybridized to a microarray having a plurality of spots containing suitable oligonucleotide probes complementary thereto. Following hybridization, colorimetric intensities of the hybridized labeled target material present at specific spots on the microarray are measured to obtain individual values which are compared with results from known control samples to accurately quantify the number of STRs in the region of interest of the DNA being analyzed.

Subjects having at least one condition selected from the group consisting of mental retardation, Down's syndrome, fragile X syndrome and autism are treated with a composition that includes gamma-aminobutyric acid agonists and / or M1 muscarinic receptor antagonists. The gamma-aminobutyric acid agonist (GABA) can be a GABA(B) agonist, such as baclofen. GABA(B) agonists can be used in combination with Group I mGluR antagonists and M1 muscarinic receptor antagonists in methods of treating humans.

Methods of increasing tonic inhibition in a subject in need thereof, for example a subject with Fragile X syndrome or Angelman syndrome are disclosed. Methods of treating secondary insomnia in a subject with a neurodegenerative disease or disorder are also disclosed. The methods can include administering the subject an effective amount of 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) or a derivative thereof, or a pharmaceutically acceptable salt thereof, increase tonic inhibition in neurons of the subject; to increase slow wave sleep (SWS) and / or slow wave activity (SWA), normalize sleep architecture, reduce secondary insomnia, increase non-rapid eye movement (NREM) sleep, increase sleep continuity, enhance delta activity within NREM, increase or improve total sleep time (TST), increase or improve sleep efficiency, reduce total time awake (TAA), reduce number of awakenings (NWA), reduce latency to persistent sleep (LPS), or to reduce wake after sleep onset (WASO), in the subject, or any combination thereof.

mGluR5 antagonists are used for the treatment and prevention of disorders, including Fragile X, autism, mental retardation, schizophrenia and Down's Syndrome. The methods of the invention can be used to treat epilepsy and anxiety in a human having Fragile X syndrome, autism, mental retardation, schizophrenia and Down's Syndrome.

mGluR5 antagonists are used for the treatment and prevention of disorders, including Fragile X, autism, mental retardation, schizophrenia and Down's Syndrome. The methods of the invention can be used to treat epilepsy and anxiety in a human having Fragile X syndrome, autism, mental retardation, schizophrenia and Down's Syndrome.

Provided herein are compositions and methods for treating a subject suffering from Fragile X syndrome, autism, Down's syndrome, mental retardation, or a neuropsychiatric condition (e.g., schizophrenia). The methods include systemic administration of a a therapeutically effective amount of a PAK inhibitor in combination with a Group I mGluR antagonist (e.g., an mGluR5 antagonist). The PAK inhibitor and mGluR antagonist can be administered together, e.g., in one pharmacological composition, or they can be administered separately.

Pharmaceutical compositions of metabotropic glutamate 5 receptor (mGlu5) antagonists or a pharmacologically acceptable salt thereof are disclosed. The compositions contain the therapeutic active compound with non-ionic polymer and ionic polymer, binder and fillers in either matrix pellet, matrix tablet or coated pellets. The compositions provide a pH-independent in vitro release profile with NMT 70% in one hour, NMT 85% in 4 hour, and NLT 80% in 8 hours. The compositions are useful for the treatment of CNS disorders, such as Treatment-Resistant Depression (TRD) and Fragile X Syndrome.

mGluR5 antagonists are used for the treatment and prevention of disorders, including Fragile X, autism, mental retardation, schizophrenia and Down's Syndrome. The methods of the invention can be used to treat epilepsy and anxiety in a human having Fragile X syndrome, autism, mental retardation, schizophrenia and Down's Syndrome.

This invention provides compounds, compositions and methods for treating Autism Spectrum Disorders (ASD) using glycyl-2-methylprolyl-glutamic acid (G-2-MePE) and analogs thereof. Autism Spectrum Disorders include Autism, Autistic Disorder, Asperger Syndrome, Childhood Disintegrative Disorder, Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), Fragile X Syndrome, and Rett Syndrome. Compositions containing compounds include water-soluble formulations, water-in-oil micro-emulsions, water-in-oil coarse emulsions, water-in-oil liquid crystals, nanocapsules, tablets, and orally administered gels. The compounds and compositions of this invention can be administered intravenously, intraventricularly, parenterally, or orally, and can be effective in treating neurodegeneration, promoting neurological function, treating seizure activity and other symptoms of ASD, and can prolong life in animals including human beings having Autism Spectrum Disorders.

The invention provides a detection kit and system for detecting the fragile X chromosome syndrome. The detection kit comprises a Q amplification system agent and a TP amplification system agent, wherein the Q amplification system agent comprises amplification primers FMR1-F and FMR1-QR, and a TP amplification system comprises amplification primers TP and TP-R. By means of the detection kit and system, Q amplification and IP amplification can be conducted, the different primers are used for detecting templates with high GC multiplicity, thus the amplification system is optimized, and high-sensibility capillary electrophoresis is combined and used, so that 200 or more CGG repeats can be detected, and thus the accuracy is high.

The invention provides a clinic rapid PCR detection kit of a fragile X syndrome. The kit comprises DNA polymerase, dNTPs, a primer group and a buffer system. The kit is used for detecting the copy number of the FMR-1(CGG)n fragment of the virulence gene of the fragile X syndrome, so the content range of the copy number can be deducted, and the carriers and patients of the virulence gene can be fast found; and the kit can be used in antenatal diagnosis and infant patient birth prevention in order to reduce the incidence of the fragile X syndrome.

The invention discloses an FRM1 gene CGG sequence repeat detection method and application. The FRM1 gene CGG sequence repeat detection method is characterized by including the following implementation steps that two pairs of primers are designed and respectively internal reference primers and detection primers, one pair of internal reference primers are located at the 5' end of a CGG repeat region, and the other pair of detection primers cross over the whole GGG repeat region; when the number of CGG repeats in the region covered with the detection primers ranges from 0 to 200, a (470+3n)bp fragment is added, wherein n is the number of the CGG repeats; when the number of CGG repeats in the region covered with the detection primers is larger than 200, the reaction is limited by the experiment condition, no fragment is added. By the adoption of the technology, two different products are added in the same reaction system, and sample genetypes are identified through comparison of the products with DNA markers. The method can be used for detecting the FRM1 gene CGG sequence repeats, can assist people in rapidly and conveniently finding carriers and patients with fragile X syndrome disease genes, and can be applied to prenatal diagnosis, make pregnant women abort infants with a fragile X syndrome, and reduce morbidity of the fragile X syndrome.

Compositions and methods for identifying and / or modulating RNA transcripts and / or genes involved in fragile X syndrome and other associated disorders are provided. In particular, RNA targets for fragile X mental retardation protein (FMRP) have been identified by a novel monoclonal antibody to FMRP and a consensus sequence for the RNA binding region has been identified. Arrays for identifying compounds, proteins, nucleotides, and the like that modulate the RNA targets or associated genes are provided. Additionally, methods for modulating RNA targets are provided.

The present invention includes a rapid, selective, and accurate method of diagnosing a human subject with a triplet repeat genetic disorder of the FMR1 gene that leads to fragile X syndrome. The present invention also includes a rapid, selective, and accurate method of diagnosing a human subject at risk for developing a triplet repeat genetic disorder of the FMR1 gene that leads to fragile X syndrome, or at risk of passing such a disorder on to their progeny.

The invention discloses a primer set and a kit for detecting a fragile X syndrome. The kit comprises the primer set for detecting the fragile X syndrome, wherein the primer set comprises a forward primer F and a reverse primer R for detecting the CGG repeat number as well as the forward primer F and a reverse primer M for detecting AGG insertion information; the sequence of the forward primer F is as shown in SEQ ID NO: 1, and FAM fluorescence is formed at 5' end of the forward primer F; the sequence of the reverse primer R is as shown in SEQ ID NO: 2; the sequence of the reverse primer M is as shown in SEQ ID NO: 3. The kit can detect whether a sample is carried by front mutation or full mutation, thereby avoiding missing detection. A method is simple to operate, convenient, quick and low in cost. The kit has stronger specificity and higher sensitivity, and has larger application prospect.

The disclosure relates to methods and compositions for reactivating a silenced FMR1 gene. In some aspects, methods described by the disclosure are useful for treating a FMR1-inactivation-associated disorder (e.g., fragile X syndrome).

Subjects having at least one condition selected from the group consisting of mental retardation, Down's syndrome, fragile X syndrome and autism are treated with a composition that includes Formula I.

The invention provides a PCR kit used for detecting the CGC replication number and AGG insert information of fragile X syndrome. The PCR kit comprises a DNA polymerase emboitement, a PCR reinforcing agent, a primer group and a correction Marker; and the primer group comprises primers F and R used for detecting the CGG replication number, and detection primers M1 and R1 and verification primers M2 and F1 used for detecting the AGG insert information. The kit can accurately and rapidly analyze the CGC replication number and the AGG insert information of a sample, can breakthrough the problems of high sequencing difficulty, long time and high cost of present fragile X syndrome detection methods adopting a fluorescence probe, MLPA and Southern Blot, and can directly analyze the range of the CGC replication number and the AGG insert information according to a gel electrophoresis result in order to rapidly diagnose the characteristics of the sample; and the product resolution can be obtained by separating products through a high-resolution device, and the CGC replication number and the AGG insert information are obtained through a mathematic model.