83 results about "Rett syndrome" 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.

The present application relates to compounds of formula (I), and their pharmaceutical compositions / preparations. This application further relates to methods of treating Rett syndrome and / or one or more symptoms associated with Rett syndrome, FOXG1 syndrome and / or one or more symptoms associated with FOXG1 syndrome, CDKL5 deficiency disorder (CDD) and / or one or more symptoms associated with CDD, or CHD8-related neurodevelopmental disorder (CHD8-NDD) and / or one or more symptoms associated with CHD8-NDD, chronic heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), or heart failure with mid-range ejection fraction (HFmrEF).

The present invention relates to a MeCP2 gene-specific trans-splicing ribozyme, and a use thereof. The trans-splicing ribozyme according to the present invention replaces the RNA of a mutant MeCP2 gene, which causes Rett syndrome, with a wild type MeCP2 RNA, so as to reduce the expression of the mutant MeCP2 protein and increase the expression of the wild type MeCP2 protein, and enables regulated expression so that wild type MeCP2 expression can be prevented from exceeding physiological levels, and thus can be effectively used for preventing or treating Rett syndrome.

Disclosed are compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein each of A, V, X, Y, Z, R7, R8, R9, R10, R11, R12, R19, R20, R21, R22, R4, m, I and n is defined herein, and their use in the treatment of Rett syndrome and / or one or more symptoms associated with Rett syndrome, FOXG1 syndrome and / or one or more symptoms associated with FOXG1 syndrome, CDD and / or one or more symptoms associated with CDD, CHD8-NDD and / or one or more symptoms associated with CHD8-NDD, chronic heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), or heart failure with mid-range ejection fraction (HFmrEF).

Aspects of the disclosure relate to the discovery that exon skipping in the MeCP2 gene can lead to a therapeutically relevant increase in MeCP2 protein, including an increase in the E1 isoform of MeCP2. Exon skipping can be achieved through antisense oligonucleotides that may be chemically modified.

The invention belongs to the field of pathologies affecting the central nervous system: in particular, severe cerebral pathologies, more particularly those restricted by the presence of the blood-brain barrier (BBB): gliomas, cerebral metastases, neurodegenerative diseases (e.g. Alzheimer's, Parkinson's or ALS), genetic diseases (Huntington's, myopathies, Leigh syndrome, Rett syndrome), but also to the field of cancers, musculoskeletal and immunological disorders, vascular diseases (thrombus) in numerous organs (e.g. liver, kidney or muscle) and in combination with numerous therapeutic approaches (e.g. chemotherapy, immunotherapy, targeted therapy or gene therapy). The invention relates to a microbubble comprising a fluorinated polymer or copolymer and a fluorinated gas, to the use thereof and also to the polymer or copolymer intermediate compounds.

The invention provides application and a method for repairing growth defects of neuronal dendrites by using ribonuclease RNase H. In particular, ribonuclease RNase H can be used as an R-loop degradation agent for treating and / or preventing neuron dendritic growth defects and related diseases thereof. A Rett syndrome cell model is utilized, and it is found that growth of dendrites can be restored by expressing ribonuclease RNase H of mammals. The method disclosed by the invention provides a very significant means for treating and preventing the Rett syndrome and other neuronal dendritic growth defect related diseases.

New 3-phenoxy-3-phenylpropanamine derivatives, compositions thereof and their use as a medicament in the treatment of nervous system disorders associated with cognitive deficits and behavioural dysfunctions, in particular fragile X syndrome and Rett syndrome.

The invention discloses a substituted heterocyclic compound containing an α-ketone skeleton and a use thereof, and relates to the field of pharmaceutical chemistry, and specifically relates to a substituted heterocyclic compound containing an α-ketone skeleton or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing these compounds and their medical uses, in particular, an application of the substituted heterocyclic compound as a fatty amide hydrolase (FAAH) inhibitor in the preparation of a drug for preventing or treating diseases related to FAAH, including inflammatory diseases, rheumatoid arthritis, hepatitis, liver fibrosis, autoimmune diseases, pain, depression, pain-depression comorbidity, autism, social phobia, Tourette syndrome, neurodegenerative diseases, anxiety post-traumatic stress (PTSD), cannabinoid use disorder, drug withdrawal, and anti-tumor treatment.

ZnCl2 co-crystal of racemic-(±)-blarcamesine hydrochloride of formula 2a, ZnCl2 co-crystal of (S)-(−)-blarcamesine hydrochloride of formula 2b and ZnCl2 co-crystal of (R)-(+)-blarcamesine hydrochloride of formula 2c, processes for preparation thereof and pharmaceutical preparation thereof and methods of treating neurodegenerative, neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease dementia and / or Rett syndrome.

Provided are the use of a ribonuclease RNase H in repairing growth defects of neuron dendrites, and a method therefor. Specifically, the ribonuclease RNase H can be used as an R-loop degradation agent for treating and / or preventing growth defects of neuron dendrites and related diseases thereof. By means of utilizing a Rett syndrome cell model, it is found that expressing the mammalian ribonuclease RNase H can restore the growth of dendrites, thus providing means of great significance for treatment and prevention of the Rett syndrome and other diseases related to growth defects of neuron dendrites.

To provide nucleic acids (including AAV expression cassettes), AAV vectors, and compositions for use in methods of treating and / or delaying the onset of diseases associated with mutations in mecp2 genes, such as Rett Syndrome.SOLUTION: Also provided herein are methods for treating a brain-derived neurotrophic factor (BDNF) - associated disease and / or delaying the onset of a brain-derived neurotrophic factor (BDNF) - associated disease. The present disclosure provides a nucleic acid comprising an adeno-associated virus (AAV) expression cassette, wherein the AAV expression cassette comprises, in a 5' to 3' direction, a 5' inverted terminal repeat (ITR), a synthetic activity-dependent promoter, a Rett syndrome-associated gene, and a 3' ITR.SELECTED DRAWING: None

The invention provides an application and a method for repairing neuronal dendritic growth defects by using ribonuclease RNase H. In particular, ribonuclease RNase H can be used as an R-loop degradation agent for treating and / or preventing neuron dendritic growth defects and related diseases thereof. By using a Rett syndrome cell model, it is found that the growth of dendrites can be restored by expressing ribonuclease RNase H of mammals. And a very significant means is provided for the treatment and prevention of Rett syndrome and other neuronal dendritic growth defect related diseases.

The present invention recognizes that there is a need for the prophylaxis or treatment of Autism Related Disorders, which includes but is not limited to Autism Spectrum Disorder, Autism, Autistic Disorder, Asperger Syndrome, Rett Syndrome Fragile X syndrome, Phelan-McDermid Syndrome, Angelman Syndrome, Pitt Hopkins Syndrome, Prader-Willi Syndrome, or combinations thereof. A first aspect of the present invention generally relates to methods of prophylaxis or treatment of Autism Related Disorders using various pharmaceutical compositions. A second aspect of the present invention generally relates to pharmaceutical compositions used for the prophylaxis or treatment of Autism Related Disorders.

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.

MeCP2 based therapy. The present invention relates to synthetic polypeptides that are useful in the treatment of disorders associated with reduced MeCP2 activity, including Rett syndrome. The present invention provides synthetic polypeptides comprising: i) an MBD amino acid sequence showing at least 70% similarity with the amino acid sequence as depicted in SEQ ID NO: 1; and ii) an NID amino acid sequence showing at least 70% similarity with the amino acid sequence as depicted in SEQ ID NO: 2, wherein the polypeptide has a deletion of at least 50 amino acids, when compared to the full length MeCP2 e1 and e2 sequences. The invention further provides nucleic acid constructs, expression vectors, virions, pharmaceutical compositions, and cells providing polynucleotides of the invention. The invention further provides methods of treating or preventing disease in an animal comprising administering to said animal a synthetic polypeptide according to the invention.

Use of a substituted purine compound or a pharmaceutically acceptable salt thereof for treating one or more of autism spectrum disorder (ASD), Rett syndrome (RTT), and Fragile X syndrome (FXS). A method for treating one or more of ASD, RTT, and FXS comprising administration of a substituted purine compound or a pharmaceutically acceptable salt thereof. Use of a substituted purine compound or a pharmaceutically acceptable salt thereof in the preparation of a pharmaceutical for the treatment of one or more of ASD, RTT, and FXS. A pharmaceutical dose of a substituted purine compound or a pharmaceutically acceptable salt thereof for use in the treatment of one or more of ASD, RTT, and FXS in a subject, wherein the dose comprises 5 to 1000 mg / kg, preferably 10 to 600 mg / kg, more preferably 25 to 100 mg / kg, most preferably about 40 mg / kg of the substituted purine compound or a pharmaceutically acceptable salt thereof.

To provide treatment or preventive medication for autism spectrum disorder. [Solution] The present invention provides a PDE10A inhibitor for treating or preventing autism spectrum disorder. The inhibitor is 1-[2-fluoro-4-(1H-pyrazole-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazole-5-yl)pyridazine-4(1H)-one or a salt thereof, and is a therapeutic or prophylactic agent for autism spectrum disorder selected from the group consisting of childhood disintegrative disorder, Rett syndrome, Cleefstra syndrome, Pitt-Hopkins syndrome, Angelman syndrome, Kabuki syndrome, Asperger syndrome, Heller syndrome, and pervasive developmental disorder.

Provided herein, inter alia, are expression systems capable of modulating expression of MECP2. In embodiments, the expression systems silence the expression of endogenous MECP2 and induce expression of recombinant MECP2. The expression system provided herein may be useful for treating a genetic disorder such as Rett Syndrome.

The present invention relates to a C-17 carbonyl-substituted oleanane triterpene derivative, a preparation method therefor, and a use thereof. Provided are a C-17 carbonyl-substituted oleanane triterpene derivative, a use of the compound in the preparation of an NRF2 activator, and preparation of a medicament for treating / preventing diseases. The diseases comprise cerebral small vascular disease, mitochondrial encephalomyopathy, autism spectrum disorder, Rett syndrome, Friedreich ataxia, stroke, hemorrhagic cerebral apoplexy, ischemic cerebral apoplexy, multiple sclerosis, amyotrophic lateral sclerosis, schizophrenia, schizophrenic cognitive impairment, Parkinson's disease, cognitive impairment in Parkinson's disease, Alzheimer's disease, vascular dementia, epilepsy, Huntington's disease, heart failure, myocardial infarction, renal failure, kidney ischemia, etc., or other disease states and conditions which are obvious to a person skilled in the art. Also provided are a prodrug thereof, or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, and a pharmaceutical composition containing same.

The present invention concerns a composition for use in, or for the treatment of, Rett syndrome, which proposes a repositioning of an anti-asthmatic drug that acts as an antagonist of leukotriene receptors, in particular of the cysteinyl-leukotriene receptor type 1 (CysLTl).

The present invention features a method of reducing tactile dysfunction or anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett Syndrome, or Fragile X syndrome by administering a GABAA agent having reduced blood brain barrier or by expressing a nucleic acid encoding an exogenous alpha or beta subunit of a GABAA receptor in dorsal root ganglion neurons in the subject using a vector.

Providing AAV-mediated targeting of miRNAs in the treatment of X-linked disorders. [Solution] This disclosure relates to the targeting of miRNAs to activate the expression of genes on an inactivated X chromosome. This gene therapy is useful for treating X-linked disorders, including Rett syndrome. This disclosure provides a novel gene therapy approach for treating X-linked disorders, such as Rett syndrome, which is caused by X-linked loss-of-function mutations. Polynucleotides and gene therapy vectors targeting one or more miRNAs known to inactivate one or more genes on the X chromosome are provided herein. The polynucleotides and vectors disclosed herein are designed to inhibit miRNAs and thereby reactivate the wild-type gene of interest on the X chromosome that has been inactivated.

Provided is a prophylactic or therapeutic agent for Rett syndrome. The prophylactic or therapeutic agent for Rett syndrome contains a PDE5 inhibitor.

A compound is represented by Formula (I), in which each carbon atom of a glycerol backbone optionally has one or more substituents, and R1 is optionally having one or more substituents, in which * is an oxygen atom bound to R1.

A kit for determining a disease state of Rett syndrome includes a reagent for detecting a gene included in the mitochondrial genome, in a sample collected from a subject.

The present invention relates to the use of cannabidiol (CBD) for the treatment of seizures associated with rare epilepsy syndromes. In particular the seizures associated with rare epilepsy syndromes that are treated are those which are experienced inpatients diagnosed with Rett syndrome. In a further embodiment the types of seizures include tonic, tonic-clonic, absence seizures and focal seizures with impairment. Preferably the dose of CBD is between 5 mg / kg / day to 50 mg / kg / day.

The present invention features a method of reducing tactile dysfunction or anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett Syndrome, or Fragile X syndrome by administering a GABAA agent having reduced blood brain barrier or by expressing a nucleic acid encoding an exogenous alpha or beta subunit of a GABAA receptor in dorsal root ganglion neurons in the subject using a vector.