89 results about "HL - Hearing loss" patented technology

Provided are compositions and method for prophylaxis and / or therapy of hearing loss or related dysfunctions, including but not limited to tinnitus, that could be ameliorated by restoring central nervous system inhibitory synapses. The compositions include polynucleotides and viral vectors that are used to express at least one GABA receptor component which may be a GABAA receptor alpha 1 subunit or GABAR receptor Ib subunit. Expression of the GABA receptor may be under control of a CaMKII promoter.

The present disclosure provides a construct comprising a coding sequence operably linked to a promoter, wherein the coding sequence encodes a vascular endothelial growth factor (VEGF) binding agent or a portion thereof. In some embodiments, a construct is an AAV construct. In some embodiments, an AAV construct is a part of an AAV particle. Compositions comprising constructs and AAV particles described herein can be useful in treating hearing loss, for example, hearing loss associated with vestibular schwannoma.

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 an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.

The present disclosure provides SL26A4 promoters and SLC26A4 enhancers, as well as vectors containing the same, that can be used to limit gene expression to cells expressing SLC26A4 and to increase gene expression in these cells, such as interdental cells, root cells, helicoid cells, and vestibular supporting cells. The SLC26A4 enhancers and SLC26A4 promoters described herein can be operably linked to polynucleotides encoding expression products, such as transgenes, and are used to treat subjects suffering from or at risk of developing hearing loss or vestibular dysfunction.

A genetically modified non-human animal lacking the expression of Klhcd7b is described. Methods and compositions for disrupting, deleting, and / or replacing the Klhcd7b coding sequence are described. Genetically modified mice useful as models of hearing loss or extremely severe deafness are also described. Loss of function cells, tissues, and embryos genetically modified to include Klhcd7b are also described.

The present invention relates to a mitochondrial permeability transition pore (mPTP)-targeting composition for treating hearing loss, and, more specifically, uses a compound, or a pharmaceutically / sitologically acceptable salt thereof, which targets the mitochondrial permeability transition pore (mPTP) to inhibit the activity or opening thereof, and thus can effectively prevent, alleviate, or treat hearing loss caused by mPTP opening.

The invention relates to a method for associating gene mutation points with specific physiological characteristics. The method comprises the following steps: receiving a sequenced test gene sequence from a human gene database; taking out a test sequence fragment with the gene length equal to the window length from the test gene sequence by adopting a sliding window with the window length; analyzing the test sequence fragments by using the prediction model; based on the analysis, determining whether the test sequence fragment is associated with a specific physiological feature; and determining that the test gene locus located at the center of the test sequence fragment is a gene mutation point associated with the specific physiological feature in response to judging that the test sequence fragment is associated with the specific physiological feature.

The present disclosure relates to compounds that act as inhibitors of NLRP3 inflammasomes; pharmaceutical compositions comprising the compounds; and methods of treating disorders associated with inflammation and inflammaging, including hearing loss and other diseases associated with aging; wherein the inhibitors of NLRP3 inflammasomes are compounds of Formula VII:or a pharmaceutically acceptable salt thereof.

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 application of an adenine base editor in DFNA15 deaf mice, and belongs to the technical field of hearing loss treatment. The invention provides nine types of novel ABE fusion proteins, namely SchABE8e, SchABE8e-N108Q, SchABE9, SchABE8e, SchABE8e-N108Q and SchABE9. The reagent is composed of SpeABE8e, SpeABE8e-N108Q, SpeABE9, SpeABE8e, SpeABE8e-N108Q, the invention relates to the technical field of chemical engineering, in particular to the chemical engineering of Sha2ABE8e, Sha2ABE8e-N108Q, Sha2ABE9 and Sha2ABE8e-N108Q. The fusion protein comprises an SchCas9 nuclease nick enzyme and a TadA-8e deaminase, wherein the amino acid sequence of the SchCas9 nuclease nick enzyme is SEQ ID NO. 19, and the amino acid sequence of the TadA-8e deaminase is SEQ ID NO. The amino acid sequence of the TadA-8e deaminase is as shown in SEQ ID NO. 20. The invention provides a novel base editing tool with wide targeting range, high editing activity and smaller size, and provides more powerful support for gene therapy research of hereditary diseases. The screened SchABE8e base editor is comprehensively tested on an endogenous target spot, and the accurate and efficient editing performance of the SchABE8e base editor is verified through multiple dimensions such as editing efficiency, an editing window, product purity, indels and off-target activity. The wide targeting range of the editor enables the editor to be suitable for gene therapy research of various hereditary diseases.

This invention relates to a recombinant adeno-associated virus (rAAV) vector encoding connexin 26 (CX26). The invention further relates to the use of the AAV vector in the treatment of hereditary hearing loss.

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.

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 an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.

The present invention relates to a viral vector comprising an EF1a promoter and expressing MPZL2, and a pharmaceutical composition for preventing or treating hearing loss comprising the same. The application of the recombinant virus vector provides a fundamental treatment strategy for hereditary hearing loss caused by Mpzl2 mutation in the absence of an effective treatment method at present.

The invention discloses an application of harpagide in preparation of a medicine for inhibiting STUB1. The harpagide can be used as a specific inhibitor of E3 ubiquitin ligase STUB1. By inhibiting the STUB1, the harpagide can effectively block the GR ubiquitination process mediated by the STUB1, so that the GR is prevented from being degraded by the proteasome, and the stability of the GR protein level is finally realized. Through combined application of harpagide and glucocorticoid, the treatment effect of hormone in a noise-induced hearing loss animal model can be remarkably improved, and the treatment effect is better than that of treatment by independently using hormone.

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

The present disclosure provides methods of preventing and / or treating hearing loss in an individual comprising administering to the individual a composition comprising an agent that increases the expression and / or activity of a Pou4f3 protein. The present disclosure also provides methods of preventing and / or treating a vestibular disorder in an individual comprising administering to the individual a composition comprising an agent that increases the expression and / or activity of a Pou4f3 protein.

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.

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.

Provided herein are compositions comprising at least two different nucleic acid vectors and the use of these compositions to treat hearing loss in a subject, wherein each of the at least two different vectors comprises a coding sequence encoding a different portion of a protein orthodontic protein.

In certain embodiments the present invention provides a method of treating hearing loss comprising: (a) administering a gene suppression agent that suppresses both copies of an endogenous gene causing the hearing loss; and (b) administering an exogenous wild-type allele engineered to resist suppression by the gene suppression agent.The present invention provides in certain embodiments a method of treating a genetic hearing loss (GHL) in a patient in need thereof comprising: (a) identifying a mutation in a GHL-causing gene, wherein the mutation causes GHL in the patient; and (b) administering to the patient a pharmaceutical composition comprising a therapeutic miRNA and a pharmaceutically acceptable carrier, wherein the GHL therapeutic miRNA is of 18 to 25 nucleotides in length and knocks-down the GHL-causing gene function at a higher level than it knocks-down gene function in a corresponding wild-type gene.

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.

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.

The present disclosure provides methods for inducing cell cycle reentry of postmitotic cell. The present disclosure further provides cells and compositions for treating diseases, such as cardiovascular diseases, neural disorders, hearing loss, and diabetes.

The present invention relates to a recombinant adeno-associated virus (rAAV) vector encoding a connexin 26 (CX26). The invention also relates to the use of said AAV vector in the treatment of hereditary hearing loss.

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 provides an application of an expression inhibitor of Gadd45a in preparation of a medicine for preventing or reducing the ototoxicity of cis-platinum. In-vivo and in-vitro experiments prove that by locally applying the Gadd45a inhibitor, cochlea hair cells and auditory functions can be effectively protected by activating autophagy, inhibiting an NF-kappaB1 inflammation pathway and regulating JNK-mediated apoptosis, so that hearing loss caused by cis-platinum is relieved. The invention provides a brand-new effective medicine product and a treatment strategy for clinically preventing and treating the ototoxicity of cis-platinum, and has important clinical application value for preventing or relieving the ototoxicity of a patient receiving cis-platinum chemotherapy.

The invention discloses application of RNA (Ribonucleic Acid) binding protein HuR and a gene of the RNA binding protein HuR as a target spot in screening of a medicine for treating senile deafness, belongs to the technical field of genetic engineering, and provides application of the RNA binding protein HuR gene as a therapeutic target spot in screening of a medicine for preventing or treating senile deafness. The RNA binding protein HuR is used as a therapeutic target to screen the medicine for preventing or treating the senile deafness. According to the application disclosed by the invention, the HuR is knocked out from the inner ear hair cells and the whole cochlea of the mouse by utilizing Atoh1-Cre and Pax2-Cre mice respectively, and the condition that the degeneration of static cilia is caused by the deletion of the HuR in the hair cells is found, so that the hair cell senescence is accelerated, and the premature hearing loss is further caused. The results show that the HuR plays an important role in maintaining a static cilia steady state, delaying hair cell senescence and preventing senile deafness, and provides a therapeutic target for clinically preventing and improving hearing loss of senile deafness patients.

The application discloses application of an Rps14 gene, a medicine and a construction method of a mouse model, belongs to the technical field of biotechnology, and the nucleotide sequence of the Rps14 gene is shown as SEQ NO. 1; compared with the prior art, the specific Rps14 transgenic mouse with a loxp site provided in the application can be used for specifically studying functions and effects of Rps14 overexpression at different sites. Specific overexpression of Rps14 in Lgr5 positive inner ear stem cells can promote significant increase of ectopic hair cells, and effective effects can be used for promoting structural and functional repair after hair cell damage and for improving hearing loss. Rps14 can be synergistically regulated with other reported inner ear genes, for example, Atoh1, Gfi1, Pou3f4 and the like, and effectively promote more ectopic hair cell proliferation and functional maturation.

A method for treating hearing loss in a subject in need thereof is provided. The method includes providing a combination of transcription factors to induce generation of a hair cell-like cell, thereby treating the hearing loss in the subject. The generated hair cell-like cells exhibit characteristic of mature functional cells that is useful in cell replacement therapy for autologous transplantation.