32 results about "Fragile x" patented technology

This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those derivatives and methods of using those derivatives or compositions in treating cognitive impairment associated with CNS disorders. It also relates to the use of an α5-containing GABAA receptor agonist (e.g., an α5-containing GABAA receptor positive allosteric modulator) in treating cognitive impairment associated with CNS disorders in a subject in need or at risk thereof, including age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI, Age-Associated Memory Impairment, Age Related Cognitive Decline, dementia, Alzheimer's Disease (AD), prodromal AD, PTSD, schizophrenia, bipolar disorder, ALS, cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease, autism spectrum disorders, fragile X disorder, Rett syndrome, compulsive behavior, and substance addiction. It also relates to the use of an α5-containing GABAA receptor agonist (e.g., an α5-containing GABAA receptor positive allosteric modulator) in treating brain cancers (including brain tumors, e.g., medulloblastomas), and cognitive impairment associated therewith.

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.

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 present disclosure relates generally to the treatment of Fragile X Syndrome using a recombinant fusion polypeptide comprising or consisting of a cell penetrating polypeptide, such as HIS or tat, and a Fragile X Mental Retardation protein (FMRP (298)).

A compound of Formula (6): Formula (8): and Formula (10): are prepared and found useful in the treatment and / or prevention of diseases and conditions such as Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, fetal alcohol exposure, autism, schizophrenia, traumatic brain injury, stroke, addictions, Huntington's disease, Fragile X and Rett's syndrome.

Methods of reactivating transcription of a fragile X mental retardation 1 (FMR1) gene and treating FMR1-associated diseases are provided. Compositions and kits for doing same are also provided.

Methods of treating developmental disorders such as Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor / ataxia syndrome (FXTAS), Autism 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.

This disclosure relates to uses of inhibitors of YTH family proteins in the management of fragile X syndrome, fragile X-associated disorders, cognitive disorders, developmental disorders, or central nervous system (CNS) disorders. In certain embodiments, this disclosure relates to treating fragile X syndrome, fragile X-associated disorders, cognitive disorders, developmental disorders, or central nervous system (CNS) disorders by administering an effective amount of an inhibitor of YTHDF1 to a subject in need thereof. In certain embodiments, the YTHDF1 inhibitor is a small molecule inhibitor such as salvianolic acid C, derivatives, prodrugs, esters, or salts thereof.

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.

Fragile X Mental Retardation protein (FMRP) is an RNA-binding protein (RBP) that controls translation of select mRNAs. We discovered that endoplasmic reticulum (ER) stress induces phosphorylation of FMRP on a site that is known to enhance translation inhibition of FMRP-bound mRNAs. We show ER stress-induced activation of inositol requiring enzyme-1 (IRE1), an ER-resident stress-sensing kinase / endoribonuclease, leads to FMRP phosphorylation and to suppression of cholesterol efflux from macrophages and apoptotic cell clearance (efferocytosis) by macrophages. Conversely, FMRP-deficiency and pharmacological inhibition of IRE1 kinase activity enhances cholesterol efflux and efferocytosis, reducing atherosclerosis in mice. Our results provide IRE1 inhibition as a promising new therapeutic approach to delaying progression or treating atherosclerosis.

Described herein is a EZH2 antisense oligonucleotide (ASO) epigenetic modulator of fragile X messenger ribonucleoprotein 1 (FMRI), its pharmaceutical compositions, and methods of treating a fragile X-associated disorder with the enhancer of zeste homolog 2 (EZH2) ASO. Also includes are pharmaceutical compositions including the EZH2 ASO and an ASO that decreases splicing between Exons 1 and 2 of FMR1-217. Methods of treating a fragile X-associated disorder with an EZH2 ASO and an ASO that decreases splicing between Exons 1 and 2 of FMR1-2F7 are also described.

The present invention relates to a nucleic acid construct comprising a nucleotide sequence encoding two or more Fragile X Messenger Ribonucleoprotein (FMRP) isoforms, which also finds application in the development of AAV vectors that lead to the successful (in vivo) expression of two or more FMRP isoforms and the beneficial results which are produced by the application of such therapy in terms of improved cognitive and / or behavioural symptoms of Fragile-X Syndrome.

Provided herein, in various embodiments, is a method 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 reduces expression of an abnormal fragile X messenger ribonucleoprotein 1 (FMR1) gene product (e.g., FMR1-2VT). Also provided herein, in various embodiments, is a composition (e.g., a polynucleotide such as an antisense oligonucleotide or a pharmaceutical composition) for reducing expression of the abnormal FMR1 gene product.

To provide a method for treating one or more symptoms on action of fragile X-associated syndrome in a subject.SOLUTION: A method for treating one or more symptoms on action of fragile X-associated syndrome in a subject by percutaneously administering an effective dose of cannabidiol (CBD) to the subject.SELECTED DRAWING: None

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.

Described herein is a EZH2 antisense oligonucleotide (ASO) epigenetic modulator of fragile X messenger ribonucleoprotein 1 (FMRI), its pharmaceutical compositions, and methods of treating a fragile X-associated disorder with the enhancer of zeste homolog 2 (EZH2) ASO. Also includes are pharmaceutical compositions including the EZH2 ASO and an ASO that decreases splicing between Exons 1 and 2 of FMR1-217. Methods of treating a fragile X-associated disorder with an EZH2 ASO and an ASO that decreases splicing between Exons 1 and 2 of FMR1-2F7 are also described.

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.

Methods and compositions for use treating Fragile X syndrome, Angelman syndrome, Fragile X-associated tremor / ataxia syndrome, Autism Spectrum Disorder, Asperger's syndrome, Pervasive developmental disorder not otherwise characterized, Childhood Disintegrative Disorder, Williams syndrome, or Jacobsen syndrome with a compound of Formula 1 as described herein, (S)-3-amino-4-(difluoromethylenyl) cyclopent-1-ene-1-carboxylic acid, (1S,3S)-3-amino-4-(difluoromethylidene) cyclopentane-1-carboxylic acid, or vagabatrin, or pharmaceutically acceptable salts of any of the foregoing, are provided.

Administration of molindone for the treatment of the aberrant behavior and motor activity symptoms associated with autism spectrum disorders (ADS), also found in subjects diagnosed with Fragile X, tuberous sclerosis, Smith-Lemli-Opitz syndrome, and maternally-inherited duplications of the Prader-Willi / Angelman syndrome region, is disclosed.

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.

Provided herein, in various embodiments, are methods of diagnosing a subject as having, or having a propensity to develop, a fragile X-associated disorder (e.g., FXS), methods of prognosing a fragile X-associated disorder (e.g., FXS) in a subject, methods of predicting a treatment outcome of a fragile X-associated disorder (e.g., FXS) in a subject, methods of stratifying a set of subjects having a fragile X-associated disorder, methods of stratifying a population of subjects having, or having a propensity to develop, FXS, and method for assessing the efficacy of a drug for treatment of FXS. Also provided herein, in various embodiments, are assays and systems useful for performing the disclosed methods. The present disclosure also provides methods of treating a subject having FXS.

The invention discloses a nucleic acid combination for detecting a CGG sequence of an FMR1 gene, a product and application of the nucleic acid combination, and relates to the technical field of genetic disease detection. The nucleic acid composition and the product provided by the invention can be used for simultaneously detecting AGG insertion information and CGG repetition number. The detection amplification range of the nucleic acid combination and the product can cover all normal persons, brittleness X pre-mutation carriers / patients and brittleness X full-mutation carriers / patients; and the method has the characteristics of short detection time, high flux, simplicity in operation and small amount of required sample nucleic acid.