15 results about "Fragile x" patented technology

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein Ring A, Ring B, R1, R2, R3, R12, and L are as defined herein. The compounds are antagonists of the resistant (R-type) voltage-gated calcium ion channel Cav 2.3. Also disclosed are pharmaceutical compositions comprising the compounds; and the compounds for use in the treatment of diseases modulated Cav 2.3, including epilepsy, neurodegenerative conditions such as Parkinson's disease, focal, drug-resistant forms of epilepsy, and other neurological disorders such as developmental and epileptic encephalopathies and Phelan-McDermid and Fragile X syndromes.

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein Ring A, Ring B, R1, R2, R3, R12, and L are as defined herein. The compounds are antagonists of the resistant (R-type) voltage-gated calcium ion channel Cav 2.3. Also disclosed are pharmaceutical compositions comprising the compounds; and the compounds for use in the treatment of diseases modulated Cav 2.3, including epilepsy, neurodegenerative conditions such as Parkinson's disease, focal, drug-resistant forms of epilepsy, and other neurological disorders such as developmental and epileptic encephalopathies and Phelan-McDermid and Fragile X syndromes.

The invention relates to application of a fragile X intellectual disorder No.1 gene in treating or relieving osteoarthritis, and belongs to the technical field of biological medicines. Researches show that the osteoarthritis is accompanied by increase of the concentration of fragile X chromosome intellectual retardation protein in serum and increase of synovial inflammatory macrophages, the fragile X chromosome intellectual retardation protein in the synovial inflammatory macrophages aggravates the progress of the osteoarthritis, articular cavity synovial inflammatory macrophage FMRP genes are inhibited in a targeted manner, and the osteoarthritis can be used for treating osteoarthritis. A new thought is provided for prevention and treatment of osteoarthritis, a support is provided for clinical transformation, and at present, related reports for treating or relieving osteoarthritis through target intervention are not found yet.

The present invention relates to the 3-phenyl-indolin-2-one compounds (1) to (4) and pharmaceutically acceptable salts and solvates thereof, as defined herein, as well as pharmaceutical compositions containing these compounds. The compounds according to the invention are maxi-K potassium channel openers and have been found to be particularly well suited for use in therapy, including in the treatment or prevention of fragile X associated disorders, such as fragile X syndrome (I).

Provided herein, in various embodiments, are methods of treating a fragile X-associated disorder (e.g., fragile X syndrome), comprising administering to a subject in need thereof, a therapeutically effective amount of an agent that decreases expression of an aberrant fragile X messenger ribonucleoprotein 1 (FMR1) gene product (e.g., FMR1-217). Also provided herein, in various embodiments, are compositions (e.g., polynucleotides such as antisense oligonucleotides or pharmaceutical compositions) for decreasing expression of an aberrant FMR1 gene product.

The invention discloses an antisense oligonucleotide which comprises at least 10 continuous nucleotides and hybridizes with an mRNA (messenger Ribonucleic Acid) sequence transcribed by a CGG repetitive sequence in 5 'UTR (Untranslated Region) of an FMR1 gene, and the mRNA sequence contains a nucleotide sequence as shown in SEQ ID NO.2. The antisense oligonucleotide provided by the invention can recover the ovarian tissue morphology and hormone level of FMR1PM / + KI hybrid mice, provides a new thought and treatment scheme for clinical treatment of fragile X-related diseases, is expected to be developed into a new drug for clinical treatment of fragile X-related diseases, and has a good application prospect.

Disclosed are compositions for RNAi of fragile X-related protein 1 (FXR1), nanoparticles comprising the same, pharmaceutical compositions comprising the same and method of treating diseases and disorders associated with FXR1 expression in a subject in need thereof. The methods may comprise modified nucleotides, e.g., locked nucleic acids (LNAs). The methods may comprise administering a therapeutically effective amount of the disclosed compositions to a subject in need thereof, e.g., a subject suffering from a disease or disorder associated with FXR1 expression.

Methods of treating developmental disorders such as Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor / ataxia syndrome (FXTAS), Autistic Spectrum Disorder, Autism, Asperger's syndrome, pervasive developmental disorder, Childhood Disintegrative Disorder, Rett syndrome, Lanau-Kleffner Syndrome, Prader-Willi Syndrome, Tardive Dyskinesia, and / or Williams Syndrome with gaboxadol or a pharmaceutically acceptable salt thereof are provided. The methods provide therapeutic compositions that may be used to improve one or more symptoms of the developmental disorder.

The present invention provides methods for treating a genetic neurodevelopmental disorder, such as Rett syndrome or Fragile X-syndrome, comprising evaluating a subject for his / her occurrence and / or severity of symptoms and / or specific biomarker levels before administering a dosage formulation of ANAVEX2-73 to the subject, administering the dosage formulation of ANAVEX2-73 to the subject for a period of time, re-evaluating the occurrence and / or severity of symptoms and / or specific biomarker levels, and optionally modifying the dosage of ANAVEX2-73 administered to the subject based on the re-evaluation results.

The application provides a G-quadruplex RNA-based protein degradation targeting chimera as well as a preparation method and application thereof. The structural general formula of the protein degradation targeting chimera is G-L-E; wherein G is G-quadruplex RNA that specifically binds to fragile X mental retardation protein (FMRP) of mammals, E is a ligand of a small molecule E3 ubiquitin ligase, and L is a connecting arm between the G-quadruplex RNA and the ligand of the small molecule E3 ubiquitin ligase. The protein degradation targeting chimera provided by the application has greatly improved stability in an in-vivo environment and cell entry capability, and also has the capability of efficiently degrading FMRP and changing a secretion mode of cancer cells, thereby providing many conveniences for development of nucleic acid-based PROTAC drugs.

This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those benzodiazepine derivatives and methods of using those derivatives or compositions in treating cognitive impairment associated with central nervous system (CNS) disorders. In particular, it relates to the use of a α5-containing GABAA receptor agonist (e.g., a α5-containing GABAA receptor positive allosteric modulator) as described herein in treating cognitive impairment associated with central nervous system (CNS) disorders in a subject in need or at risk thereof, including, without limitation, subjects having or at risk for age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI (aMCI), Age-Associated Memory Impairment (AAMI), Age Related Cognitive Decline (ARCD), dementia, Alzheimer's Disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia, bipolar disorder, amyotrophic lateral sclerosis (ALS), cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease (PD), autism spectrum disorders, fragile X disorder, Rett syndrome, compulsive behavior, and substance addiction. It also relates to the use of a α5-containing GABAA receptor agonist (e.g., a α5-containing GABAA receptor positive allosteric modulator) as described herein in treating brain cancers (including brain tumors, e.g., medulloblastomas), and cognitive impairment associated therewith.

Methods for determining methylation status and CGG repeat extent in a untranslated region (UTR) of Fragile X messenger riboprotein gene 1 (FMR1) in a subject comprise (a) isolating high molecular weight DNA from a whole blood sample; (b) enriching the isolated DNA for an UTR of FMR1 with Cas9-assisted gene-targeted cleavage of regions of interest in the FMR1 gene and ligation of sequencing adapters to the cleaved regions of interest; and (c) sequencing the regions of interest to determine a cumulative number of methylated CGG repeats in the regions of interest and a cumulative number of CGG repeats in the regions of interest. Methods for evaluating a subject for Fragile X Syndrome further comprise (d) relating the cumulative number of CGG repeats and the cumulative number of methylated CGG repeats to a clinical phenotype of Fragile X Syndrome.

The invention belongs to the field of biological medicine, and relates to a new application of a fragile X intellectual disturbance No.1 gene, namely an application of the fragile X intellectual disturbance No.1 gene in preparation of a reagent for diagnosing osteoarthritis, and the reagent for diagnosing osteoarthritis comprises but is not limited to substances for detecting the fragile X intellectual disturbance No.1 gene or a gene product of the fragile X intellectual disturbance No.1 gene. The research shows that the osteoarthritis is accompanied by the increase of the concentration of the fragile X chromosome intellectual retardation protein in serum and the increase of the synovial inflammatory macrophages, and the fragile X chromosome intellectual retardation protein in the synovial inflammatory macrophages aggravates the progress of the osteoarthritis. The macrophage FMR1 gene for targeted inhibition of articular cavity synovitis can be used as a diagnostic marker of osteoarthritis, a new idea is provided for prevention and treatment of osteoarthritis, and a support is provided for clinical transformation.