106 results about "HL - Hearing loss" patented technology

The invention discloses an adenine base editor for DFNB9 hearing loss repair, and belongs to the field of gene therapy of hearing repair. The fusion protein comprises nNme2Cas9, and adenine deaminase TadA-8e or TadA-8e-N108Q (adenine deaminase) or TadA-8e-N108Q-L145T (adenine deaminase). The invention further discloses a preparation method of the adenine deaminase. The amino acid sequences of the TadA-8e, the TadA-8e-N108Q and the TadA-8e-N108Q-L145T are respectively as shown in SEQ ID NO. 1 to SEQ ID NO. 3. The fusion protein and a guide RNA form a base editor. Compared with the prior art, the base editor is used as a treatment means, severe deafness can be recovered to a normal level, and the effect can be maintained for at least six months after treatment. In addition, the treatment window period is relatively long, and the method has clinical transformation significance.

Systems and methods can be employed for facilitating access and procedures in the outer, middle, and inner ear in order to diagnose or treat ear disorders including, but not limited to hearing loss and excessive ear wax. In some examples, the systems and methods include instruments and techniques that facilitate trans-tympanic membrane or trans-fibrous ring access to the middle ear. The systems and methods can also be used to improve accessibility for various otological surgical procedures, such as, but not limited to, cholesteatoma removal, tympanic membrane repair and ossicular chain repair.

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 composition comprising a) a first recombinant adeno-associated viral (rAAV) vector genome comprising a first expression cassette comprising a promoter operably linked to nucleic acid sequence comprising a 5' portion of an otoferlin gene, wherein the first expression cassette is flanked by inverted terminal repeats (ITRs); and b) a second rAAV vector genome comprising a second expression cassette comprising a nucleic acid sequence comprising a 3' portion of an otoferlin gene, wherein the second expression cassette is flanked by ITRs, and wherein the composition can comprise about 4E10-9E13 vg / mL, optionally about about 4.1E10- 4.1E12 total vg or about 8.1E10-8.1E12 total vg and the use of these compositions to treat hearing loss in a subject.

The present disclosure provides SL26A4 enhancers and SLC26A4 promoters, as well as vectors containing the same, that can increase gene expression in cells expressing SLC26A4, 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.

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.

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 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.

Provided herein are compositions comprising a) a first recombinant adeno-associated virus (rAAV) vector genome (vg) comprising a first expression cassette comprising a promoter operably linked to a nucleic acid sequence comprising a 5'part of an orthodontic protein gene wherein the expression cassette is flanked by an inverted terminal repeat (ITR); and b) a second rAAV vector genome comprising a second expression cassette comprising a nucleic acid sequence comprising a 3'portion of an orthodontic protein gene wherein the expression cassette is flanked by an ITR wherein the compositions comprise about 4.1 E10-4.1 E12 total vg or about 8.1 E10-8.1 E12 total vg, and the use of these compositions to treat hearing loss in a subject.

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 relates to the technical field of medical assistance, and discloses a large vestibular aqueduct syndrome prediction model construction method and a large vestibular aqueduct syndrome prediction method.The method comprises the steps that a medical history information data set, a hearing examination data set, an iconography examination data set and a genetic examination data set are obtained, based on the medical history information dataset, the hearing examination dataset, the iconography examination dataset and the genetic examination dataset, features related to the large vestibular aqueduct syndrome are extracted respectively, and feature datasets are obtained; and training a machine learning model based on the feature data set, and obtaining a large vestibular aqueduct syndrome prediction model after training is completed. The constructed large vestibular aqueduct syndrome prediction model can provide diagnosis help for subjects who have not clear diagnosis of the large vestibular aqueduct syndrome yet, reduce missed diagnosis and misdiagnosis of the large vestibular aqueduct syndrome caused by insufficient experience of clinicians, and can also provide diagnosis assistance for subjects who have already diagnosed as the large vestibular aqueduct syndrome. A prediction of hearing loss progression is provided.

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.