34 results about "Sensorineural hearing loss" patented technology

The invention discloses a mouse cochlea radiotherapy device and a radioactive sensorineural hearing impairment animal model, and belongs to the technical field of radiotherapy hearing impairment animal models.The mouse cochlea radiotherapy device comprises a base and radiotherapy equipment arranged above the base, a lead plate is arranged below the radiotherapy equipment, a plurality of mounting boxes are fixed to the bottom end of the base, and the mounting boxes are connected with the lead plate. A mounting box is arranged on the base, a plurality of sliding grooves penetrating through the mounting box are formed in the top end of the base, a head fixing belt and two sets of limb fixing belts are arranged between the two sliding grooves on the same side, positioning teeth are arranged at the bottom ends of the head fixing belt and the limb fixing belts, and a toothed plate clamped with the positioning teeth is elastically arranged in the mounting box. According to the mouse cochlea radiotherapy device and the radioactive sensorineural hearing injury animal model, a test mouse can be conveniently fixed, and the accuracy of radioactive rays and the test effect are improved.

To provide novel therapies targeting hair cells for the treatment of sensorineural hearing loss or vestibular dysfunction.SOLUTION: The disclosure provides polynucleotides containing regions of the Myosin 15 (Myo15) promoter, as well as vectors containing the same, that can be used to promote expression of a transgene specifically in hair cells. The polynucleotides described herein may be operably linked to a transgene, such as a transgene encoding a therapeutic protein, so as to promote hair cell-specific expression of the transgene. The polynucleotides described herein may be operably linked to a therapeutic transgene and used for the treatment of subjects having or at risk of developing hearing loss or vestibular dysfunction.SELECTED DRAWING: Figure 1

Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of a stereocilin protein, and the use of these compositions to treat non-syndromic sensorineural hearing loss in a subject.

The disclosure features compositions and methods for the treatment of sensorineural hearing loss and auditory neuropathy, particularly forms of the disease that are associated with mutations in otoferlin (OTOF), by way of OTOF gene therapy. The disclosure provides a variety of compositions that include a first nucleic acid vector that contains a polynucleotide encoding an N-terminal portion of an OTOF protein and a second nucleic acid vector that contains a polynucleotide encoding a C-terminal portion of an OTOF protein. These vectors can be used to increase the expression of OTOF in a subject, such as a human subject suffering from sensorineural hearing loss.

The invention discloses application of tangeretin in preparation of a medicine for treating hearing loss. The invention proposes and verifies that the tangeretin can effectively protect the spiral ganglion neurons for the first time, and avoids the death of the cells caused by cisplatin medication; experimental data show that the preventive tangeretin drug can effectively prevent hearing loss of adult mice and greatly relieve sensorineural deafness caused by cis-platinum, and a new thought is provided for clinical ototoxicity drug administration.

Methods of treating tinnitus, acute sensorineural hearing loss, Meniere's disease, Tourette's syndrome, ADHD or addiction with (1S,3S)-3-amino-4-(difluoromethylidene) cyclopentane-1-carboxylic acid or a pharmaceutically acceptable salt thereof are provided. Methods of treating tinnitus, acute sensorineural hearing loss, Meniere's disease, Tourette's syndrome, ADHD or addiction with (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid are provided. Also provided are therapeutic compositions that may be used to improve one or more symptoms of tinnitus, acute sensorineural hearing loss, Meniere's disease, Tourette's syndrome, ADHD or addiction.

The present invention belongs to the technical field of sensorineural hearing. Provided is the use of SPTBN1 as a target in the treatment of GJB2-related sensorineural hearing loss. The use comprises: the construction of a stably transfected cell line, wherein: HEK293T cells are cultured using a DMEM culture medium supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin in a humidified incubator at 37ºC with 95% air and 5% CO2, and when the cells reach 80%-90% confluence, cell passage is performed; IP-MS analysis, wherein: protein complexes are purified using Protein A / G immunoprecipitation magnetic beads, a portion of the extracted proteins is used as input, and then 2 μg of anti-Cx26 antibody is added to the remaining protein extract, same are gently pipetted and mixed, and incubated on a rotating shaker at 4℃ overnight; immunofluorescence observation of the co-localization of Cx26 and SPTBN1, wherein: a stably transfected cell line expressing WT-Cx26 and Mut-Cx26 is constructed; and co-immunoprecipitation (Co-IP) validation, wherein: a stably transfected cell line expressing WT-Cx26 is constructed. The present invention overcomes the limitations of therapeutic methods, such as the relatively low targeting specificity and short therapeutic time windows associated with full-length protein supplementation via gene therapy, thereby providing new insight into GJB2-related hearing loss, and a new target and a new treatment for same.

Provided herein are dual vector systems for expressing a Protocadherin-15 protein or variant thereof in a subject, wherein the dual vector system comprises a first vector comprising a first coding polynucleotide that encodes an N-terminal portion of the Protocadherin-15 protein or variant thereof; and a second vector comprising a second coding polynucleotide that encodes a C-terminal portion of the Protocadherin-15 protein or variant thereof, wherein the first coding polynucleotide and the second coding polynucleotide that encode the Protocadherin-15 protein or variant thereof do not overlap.

The invention discloses a multi-layer composite artificial cochlea electrode coating material with multiple anti-inflammatory and electrode-neuron repairing functions and a preparation method of the multi-layer composite artificial cochlea electrode coating material. The preparation method specifically comprises the following steps: constructing a silver elementary substance coating on an artificial cochlea electrode platinum-iridium alloy contact base material by using a physical vapor deposition process; an electrode contact is obtained by combining a vacuum ultrashort pulse laser processing technology, and a methacrylated silk fibroin SilMA microsphere material loaded with bilirubin is prepared by a microfluidic technology; preparing gold-copper clustering enzyme by using a wet chemical reduction method; the preparation method comprises the following steps: preparing a porous methacrylated gelatin solution, composite neural stem cells, SilMA drug-loaded microspheres and gold-copper clustered enzyme; after in-situ curing and demolding are carried out on the surface of the artificial cochlea electrode by combining a mold pouring method, a multi-layer composite artificial cochlea electrode coating material with multiple anti-inflammatory and electrode-neuron repairing functions is obtained on the surface of the electrode, and the coating can provide a cell source for nerve deafness repairing and complete electrode-neuron repairing; and multiple anti-inflammatory functions are realized.

This invention provides drugs and methods for preventing or reversing hearing loss. [Solution] A composition comprising at least two different nucleic acid vectors, each of which comprises a coding sequence encoding a different portion of the otoferrin protein, and the use of these compositions for treating hearing loss in a subject are provided herein. This disclosure is based on the discovery that a composition comprising at least two different nucleic acid vectors, each of which comprises a coding sequence encoding a different portion of the otoferrin protein, can be used to generate a sequence encoding an active otoferrin protein (e.g., full-length otoferrin protein) in mammalian cells, thereby enabling the treatment of asymptomatic sensorineural hearing loss in a subject in need.

The invention discloses an application of an ECM related gene in treatment of hearing loss. Specifically, the invention provides an application of an active ingredient, and the active ingredient is used for preparing a composition for treating hearing loss. And the active ingredient comprises a down-regulating agent of an ECM-related gene selected from the group consisting of Col6a3, Ogn, Col3a1, or a combination thereof. The composition disclosed by the invention can be used for effectively treating sensorineural hearing loss caused by excessive ECM deposition.

Methods of using Fibroblast growth factor 2 (FGF2) to treat subjects with hearing loss associated with impaired word recognition.

The invention provides application of SPTBN1 as a target spot in treatment of sensorineural hearing loss related to GJB2, and belongs to the technical field of sensorineural hearing. Comprising the following steps: constructing a stably transfected cell line: culturing HEK293T cells in a humidifying incubator with temperature of 37 DEG C, 95% of air and 5% of CO2 by using a DMEM (Dulbecco Modified Eagle Medium) culture medium added with 10% of fetal calf serum and 1% of double antibodies, and performing cell passage when the cells grow to a confluence degree of 80-90%; performing IP-MS analysis: purifying a protein compound by using ProteinA / G immunoprecipitation magnetic beads, taking part of extracted protein as input, then adding 2 [mu] ganti-Cx26 antibody into the residual protein extract, slightly blowing, beating and mixing, and performing turnover shaking table incubation at 4 DEG C overnight; carrying out immunofluorescence observation on co-localization of the Cx26 and the SPTBN1; constructing a stably transfected cell line for expressing the WT-Cx26 and the Mut-Cx26; and carrying out co-immunoprecipitation (Co-IP) verification: constructing a stably transfected cell line for expressing the WT-Cx26. According to the invention, limitations of treatment modes such as relatively low complete protein targeting and short treatment time window are supplemented through gene therapy, and a new insight, a new target spot and a new treatment are provided for GJB2-related hearing loss.

The present application relates to the technical field of biological medicine, and particularly relates to a composition for protecting cochlear spiral ganglion neurons and application thereof. The composition comprises Panax notoginseng saponins (PNS) and Polygonatum sibiricum polysaccharide (PSP). Research shows that the composition can significantly improve the survival rate of neurons, promote neurite growth, reduce the level of reactive oxygen species, inhibit cell apoptosis, and promote autophagy by regulating the PI3K / AKT signaling pathway, thereby effectively resisting ototoxicity damage induced by aminoglycoside antibiotics. The present application further provides the use of the composition in the preparation of a drug for preventing or treating sensorineural hearing loss.

This disclosure provides compositions and methods for treating sensorineural hearing loss and auditory neuropathy, particularly disease forms associated with otomorphin (OTOE) mutations, using OTOE gene therapy. The disclosure provides various compositions comprising a first nucleic acid vector containing a polynucleotide encoding the N-terminal portion of an OTOE isoform 5 protein and a second nucleic acid vector containing a polynucleotide encoding the C-terminal portion of an OTOE isoform 5 protein. These vectors can be used to increase OTOE expression in subjects, such as human subjects with sensorineural hearing loss.

The present application relates to a composition using an endothelin B receptor agonist, such as Sovastatin (N-succinyl-[Glu9, Ala11, 15] endothelin 1, IRL-1620), for promoting cell proliferation and protecting the original neuroepithelium of cochlear and vestibular cells located within the ear sac. The pharmaceutical composition is systemically administered by means of tympanic membrane puncture, cochleostomy or intravenous or intramuscular injection. A pharmaceutical composition for the treatment of sensorineural hearing loss and vestibular disorders caused by inner ear cell degeneration, the pharmaceutical composition comprising a compound of an endothelin analogue, the use being treated by the neuroprotection and neurogenesis mechanism of cochlear vestibular hair cells and synapses.

The present disclosure provides compositions and methods for treating subjects at risk for or with sensorineural hearing loss by modulating the rate of Atoh1 protein degradation to increase levels of Atoh1 protein.

The invention belongs to the technical field of biological medicines, and discloses an application of rhizoma acori graminei essential oil in preparation of drugs for preventing and treating sensorineural deafness, the rhizoma acori graminei essential oil is taken as a core effective component, key active substances of the rhizoma acori graminei essential oil are determined to be beta-asarone and isomethyleugenol, and the rhizoma acori graminei essential oil can be prepared into oral preparations and / or ear drops; animal experiments and human body safety tests prove that the rhizoma acori graminei essential oil can remarkably reduce noise-induced hearing threshold displacement, protect the integrity of cochlea outer hair cells and the banding synaptic function of inner hair cells and inhibit cochlea local inflammation pathway activation, and is non-toxic to main organs and free of skin and tympanic membrane irritation. The invention solves the technical problems of poor compliance, obvious side effects on the whole body and indefinite effective components of the existing sensorineural deafness prevention and treatment medicines, and provides a safe and effective prevention and treatment scheme with strong scene adaptability.

The present invention relates to brain derived nerve factor (BDNF) for use in the prevention or treatment of sensorineural hearing loss in a subject, wherein said BDNF is administered intranasally to said subject.

The invention discloses application of cimicifugin in preparation of a medicine for preventing or treating inner ear hair cell injury, and belongs to the technical field of biological medicine. According to the invention, it is found for the first time that a natural compound cimifugin has a definite inner ear hair cell protection effect. By inhibiting hair cell apoptosis and reducing hearing synapse loss and hearing nerve fiber injury, the cimicifugin effectively relieves hair cell injury and hearing function decline caused by cis-platinum and other drugs, noise exposure and aging. The protection mechanism is related to inhibition of activation of a pro-apoptosis signal. The preferred administration mode is local administration, especially delivery through a round window membrane, and the dosage form can be a solution, a suspension or a sustained release preparation. Cell, in-vitro hair cell tissue and animal model experiments prove that the cimicifugin can obviously relieve hair cell damage and improve the auditory function. The invention provides a new drug candidate scheme for preventing and treating sensorineural hearing loss, and has important clinical application value.

The disclosure features compositions and methods for the treatment of sensorineural hearing loss and auditory neuropathy, particularly forms of the disease that are associated with biallelic missense mutations in otoferlin (OTOE), by way of OTOE gene therapy. The disclosure provides a variety of compositions that include a first nucleic acid vector that contains a polynucleotide encoding an N-terminal portion of an OTOE isoform 5 protein and a second nucleic acid vector that contains a polynucleotide encoding a C-terminal portion of an OTOE isoform 5 protein. These vectors can be used to increase the expression of OTOE in a subject, such as a human subject suffering from sensorineural hearing loss.

To provide a new therapy targeting hair cells for the treatment of sensorineural hearing loss or vestibular dysfunction.SOLUTION: The present disclose provides polynucleotides containing a region of the myosin 15 (Myo15) promoter, as well as vectors containing the same, which can be used to promote expression of a transgene specifically in hair cells. The polynucleotides described herein can be operably linked to a transgene, such as a transgene encoding a therapeutic protein, to facilitate hair cell-specific expression of the transgene. The polynucleotides described herein can be operably linked to a therapeutic transgene and used in the treatment of a subject having or at risk of developing hearing loss or vestibular dysfunction.SELECTED DRAWING: Figure 1

The disclosure features compositions and methods for the treatment of sensorineural hearing loss and auditory neuropathy, particularly forms of the disease that are associated with mutations in otoferlin (OTOF), by way of OTOF gene therapy. The disclosure provides a variety of compositions that include a first nucleic acid vector that contains a polynucleotide encoding an N-terminal portion of an OTOF protein and a second nucleic acid vector that contains a polynucleotide encoding a C-terminal portion of an OTOF protein. These vectors can be used to increase the expression of OTOF in a subject, such as a human subject suffering from sensorineural hearing loss.

The invention discloses application of triterpenoid saponin and analogues thereof in preparation of a medicine for treating senile deafness, and belongs to the technical field of biological medicine. The triterpenoid saponin and the analogue of the triterpenoid saponin comprise Chiisanoside, Divaroside, Sessiloside A1 (Sessiloside A1) or Chiisanogenin (Sessiloside A1), Sessiloside A1 (Sessiloside A1) and Sessiloside A1 (Sessiloside A1). The triterpenoid saponin and the analogues thereof provided by the invention are derived from leaves and fruits of acanthopanax senticosus and acanthopanax sessiliflorus which are rich in resources and relatively renewable, are rich in original plants or can be obtained through simple conversion, and are safe to operate and low in production cost. The triterpenoid saponin and the analogues thereof provided by the invention achieve the effect of treating the senile deafness by inhibiting ear hair cell aging, can accurately act on targets related to the senile deafness, enable the drug effect to be more direct and effective, can effectively reduce the generation of toxic and side effects, and have a good application prospect. Reference data and a new research and development thought are provided for treatment of senile senile deafness.

To provide compounds for the treatment of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, other dementia and neurodegenerative diseases, spinal cord injury, sensorineural hearing loss, and the like.SOLUTION: The present invention provides compounds that demonstrate increased stability in simulated intestinal fluid and simulated gastric fluid, but that can be hydrolyzed in plasma to produce compounds that retain base structure's beneficial properties. In one embodiment, the compound is represented by formula (I), possesses a di-amino acid core structure, and is substituted with one or more organic functional groups at the C-terminus, N-terminus, and / or the side-chain of the core.SELECTED DRAWING: None

The disclosure features compositions and methods for the treatment of sensorineural hearing loss and auditory neuropathy, particularly forms of the disease that are associated with a mutation in otoferlin (OTOF), by way of OTOF gene therapy. The disclosure provides a variety of compositions that include a first nucleic acid vector that contains a polynucleotide encoding an N-terminal portion of an OTOF isoform 5 protein and a second nucleic acid vector that contains a polynucleotide encoding a C-terminal portion of an OTOF isoform 5 protein. These vectors can be used to increase the expression of OTOF in a subject, such as a human subject suffering from sensorineural hearing loss.

The present disclosure features compositions and methods for the treatment of sensorineural hearing loss and auditory neuropathy, particularly disease forms associated with mutations in OTOF, by an Orthodontic Protein (OTOF) gene therapy. The present disclosure provides compositions comprising a first nucleic acid vector comprising a polynucleotide encoding an N-terminal portion of an OTOF protein (e.g., OTOF isoform 5 protein) and a second nucleic acid vector comprising a polynucleotide encoding a C-terminal portion of an OTOF protein (e.g., OTOF isoform 5 protein). These vectors are useful for increasing the expression of OTOF in a subject suffering from sensorineural hearing loss, such as a human subject.

Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of a stereocilin protein, and the use of these compositions to treat non-syndromic sensorineural hearing loss in a subject.

The application discloses a gene medicine for treating deafness-dystonia-optic neuropathy syndrome caused by TIMM8A gene defect and application. The medicine core is a modularly designed adeno-associated virus vector system which carries an expression cassette containing a tissue-specific promoter and a human TIMM8A treatment gene. The application realizes precise treatment through local minimally invasive injection according to different symptoms: AAV-Anc80L65-MYO15-TIMM8A is injected into the cochlea to treat sensorineural hearing loss; AAV2 / 4-Brn3b-TIMM8A is injected into the vitreous body of the eyeball to treat optic neuropathy; AAV9-hSyn-TIMM8A is injected into the central lateral ventricle to treat dystonia. Preclinical studies have confirmed that the strategy can efficiently express TIMM8A protein in the corresponding target cells, significantly repair hearing, visual and motor function defects, and correct mitochondrial dysfunction from the pathological mechanism.

Methods of treating tinnitus, acute sensorineural hearing loss, age-related hearing loss, or Meniere's disease, with a compound according to Formula (I), or a pharmaceutically acceptable salt thereof, are provided. Also provided are therapeutic compositions that may be used to improve one or more symptoms of tinnitus, acute sensorineural hearing loss, or Meniere's disease. Formula (I): or pharmaceutically acceptable salts thereof, wherein R1, R2, R7 and ring A have any of the meanings herein defined in the description.