73 results about "NAV1" patented technology

A variety of zinc finger proteins (ZFPs) and methods utilizing such proteins are provided for use in treating chronic pain. ZFPs that bind to a target site in genes that are aberrantly expressed in subjects having chronic pain are described. In addition, ZFPs that bind to a target site in genes expressed at normal levels in subjects experiencing chronic pain, modulation of whose expression results in decreased pain perception, are also provided. For example, genes that are over-expressed in the dorsal root ganglia (DRG) of pain patients (e.g., Nav1.8) can be repressed.

A variety of zinc finger proteins (ZFPs) and methods utilizing such proteins are provided for use in treating neuropathic pain. ZFPs that bind to a target site in genes that are aberrantly expressed in subjects having neuropathic pain are described. In addition, ZFPs that bind to a target site in genes expressed at normal levels in subjects experiencing neuropathic pain, modulation of whose expression results in decreased pain perception, are also provided. For example, genes that are over-expressed in the dorsal root ganglia (DRG) of pain patients (e.g., VR1, TRKA and / or Nav1.8) can be repressed, whereas genes that are under-expressed in the same populations can be activated.

The invention provides short interfering nucleic acids, either single-stranded or double-stranded, that cause RNAi-induced degradation of mRNA from the Nav1.8 sodium channel gene; to pharmaceutical compositions comprising such short interfering nucleic acids; recombinant vectors comprising such short interfering nucleic acids; a method for inhibiting translation of an mRNA; a method for inhibiting expression of a polypeptide; a method for blocking the membrane potential in a cell; a method for blocking the sodium current in a cell; and a method for inhibiting chronic pain.

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the Nav1.8 gene (Nav1.8 gene), comprising an antisense strand having a nucleotide sequence which is less that 25 nucleotides in length and which is substantially complementary to at least a part of the Nav1.8 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of the Nav1.8 gene using the pharmaceutical composition; and methods for inhibiting the expression of the Nav1.8 gene gene in a cell.

Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Nav1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Nav1.7. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

The present invention relates to antibodies and antigen binding fragments thereof derived from antibodies raised by DNA immunization of host animals, particularly camelids (e.g. llama). The antibodies and antigen binding fragments thereof bind to proteins which may be particularly large in size (at least 1115 amino acids in length), or have at least 8 transmembrane domains, or are naturally encoded by nucleotide sequences which are difficult to replicate in standard or common E. coli strains. The present invention also relates to antibodies and antigen binding fragments thereof which bind to ion channels, in particular the voltage-gated sodium channel Nav1.7. Methods of raising antibodies against particular protein targets by a process of DNA immunization are also provided.

The present invention relates to Huwentoxin-IV variants, polynucleotides encoding them, methods of making and using the foregoing, and methods of alleviating pain with peptide inhibitors of Nav1.7.

The invention relates to an application of bulleyaconitine A used for preparing medicine for treating Nav1.7 pain, which belongs to medicine containing effective organic ingredients, in particular to medicine using the bulleyaconitine A for treating a disease. The medicine contains excipient which plays roles in padding, bond, disintegration and lubrication, the bulleyaconitine A and the excipient are mixed to be pressed into tablets, and each tablet of bulleyaconitine A contains 0.1mg to 0.5mg of the bulleyaconitine A. The invention has the characteristics of rapid absorption by oral administration, low content in the brain for the medicine distributed in a body, long half life period, little toxicity, and no tolerant phenomenon or addiction.

The present invention relates to analgesic applications of a polypeptide toxin mu-EPTX-Na1a (short for Na1a) from Naja atra. According to the present invention, the Na1a provides a strong inhibition effect for the voltage-gated sodium channel subtype Nav1.8, wherein the half-maximal inhibition concentration is 167 nM; the subtype selectivity shows that the Na1a is highly specific; the pharmacodynamics activity experiment results show that the Na1a provides stronger analgesic activities in acetic acid writhing pain models, formalin pain models and complete Freund's adjuvant pain models compared to morphine, and provides similar or slightly excellent analgesic activities in hot plate pain models and sciatic nerve ligation models compared to morphine; the evaluation results of the side effects of the Na1a show that the weak side effects are provided in the movement function, the cardiotoxicity, the hemolytic activity and the cytotoxic activity; and the Na1a is the analgesic polypeptide having the application value.

The invention relates to an amino acid sequence and a gene sequence of cyriopagopus albostriatus toxin mu-TRTX-Ca1a, and application, and belongs to the field of biomedicine. The mu-TRTX-Ca1a contains38 amino acid residues, wherein six cysteines form three pairs of disulfide bonds, and the molecular weight is 4289.31 Da. The cyriopagopus albostriatus toxin mu-TRTX-Ca1a can preferentially inhibitsodium channel subtype Nav1.7. The cyriopagopus albostriatus toxin mu-TRTX-Ca1a can remarkably alleviate the pain caused by a mice formalin model, an acetic acid writhing model and a hot plate model,and can be used as a drug for treating pain.

Provided are methods for treating and / or reducing the symptoms of a neurological or neurodevelopmental disease or disorder characterized by ectopic expression of certain ion channels, in particular, the Nav1.8 subtype SCN10a sodium channel, or the KCNQ1 potassium channel, in neuronal cells of the central nervous system (CNS) of a subject by administering to a subject in need an antagonist of one or both of these ion channels, and in particular, an antagonist of SCN10a, to block, reduce, or suppress the aberrant CNS neuronal ion channel expression and / or activity and normalize behavioral and cognitive defects associated with the neurological and neurodevelopmental disease or disorder, so as to treat and / or reduce the symptoms of the neurological or neurodevelopmental disease or disorder. Examples of such diseases or disorders that may be treated by the described methods include, for example, Pitt-Hopkins Syndrome (PTHS), autism, autism spectrum disorder, schizophrenia, 18q syndrome and the like.

The invention relates to a voltage-gating sodium ion channel structure modeling method based on development coupling analysis, and belongs to the field of structural biology. The method includes the steps that through the rosetta membrane-protein homology modeling method, a eukaryon sodium ion channel NavPas (PDBid:5X0M) tertiary structure serves as a template, and four subunit structures of whicha Nav1.5 pore domain is composed are primarily established; through the development coupling analysis (DCA) method, the contact ratio between actual residue pairs and interaction residue pairs obtained after forecasting through DCA in the structures is evaluated; combined with a scoring function, the structures with the high score and the high contact ratio are selected as initiating structures of all structural domains; the four selected subunit structures are assembled and optimized; a structure capable of having the high interface contact ratio and the high RosettaMP score to meet the evaluation requirements is further selected from the optimized structures to serve as a final structure. According to the voltage-gating sodium ion channel structure modeling method based on development coupling analysis, the defects that in a traditional structure modeling method, transmembrane area information is not fully considered, the homology of a template is low, and the forecasting accuracy is poor are overcome, and the reliability is high.

The invention mainly relates to phrixotoxin (PaTx-1) extended polypeptide and application thereof. The polypeptide toxin can effectively and selectively block Nav1.7 (voltage-gated sodium channel alpha subunit group), and therefore the polypeptide toxin can serve as a selective sodium ion channel blocking agent so as to be applied to multiple aspects such as molecular mechanisms, neutral signal transmission and disease treatment relevant to Nav1.7 sodium ion channels.

The invention discloses a conotoxin, a polypeptide composition as well as a preparation method and application thereof, and relates to the technical field of cosmetic preparation. The conotoxin has a sequence as shown in SEQ ID NO. 1. Amino acid residue mutation is performed on wild mu-conotoxin PIIIA, so that the retardation effect of the mu-conotoxin on a sodium channel is moderately weakened, and meanwhile, the stability is kept under acidic and alkaline conditions, and the isoelectric point stability and the target specificity are kept. The novel conotoxin provided by the invention has the characteristics of stability, low production cost and the like. The mutated conotoxin or salt thereof keeps a relatively strong anti-wrinkle function, and the mutated conotoxin can avoid facial muscle stiffness and paralysis caused by excessive inhibition of a skeletal muscle sodium channel Nav1.4, and meanwhile, the risk of inhibiting the myocardial sodium channel and a brain sodium channel is also remarkably reduced.

The present invention provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders, cough, and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

The invention provides a cell line capable of stably expressing 6His-Nav1.1 fusion protein and construction. The cell line is prepared by transfecting an HEK293 cell with a recombinant vector carryinga sequence shown in SEQ ID No.3. The cell line can stably express the 6His-Nav1.1 fusion protein with bioactivity, Nav1.1 is easier to purify and enrich by the aid of a 6His label carried by the protein, a biological recognition aglucone and a toxicity research target are provided for Nav1.1 ion channel research, high-throughput screening of new drugs and unknown toxins, and an important biological affinity material is provided for screening, separation and identification of nerve drugs and neurotoxins. Meanwhile, a core raw material is provided for development of biosensors and establishmentof a high-throughput screening technology.

The invention provides an antibody or an antibody fragment of a targeted cell membrane voltage-gated sodium channel alpha subunit Nav1.7, and the specific binding target of the antibody or the antibody fragment is an ion-conducting pore module (PM) of an S3 structural domain of an IV structural domain (Domain IV) of the voltage-gated sodium channel alpha subunit. The antibody or the antibody fragment thereof can inactivate the ion-conducting pore module so that sodium ions cannot normally enter nerve cells, and the effect of treating and relieving pain is achieved.

The invention discloses an analgesic and antipruritic pharmaceutical composition and an application method thereof, and belongs to the technical field of medical chemistry. The research of the invention finds that the analgesic effect generated by independently inhibiting the activity of Nav1.7 or Nav1.8 is reduced along with the time history of peripheral nerve injury, and also finds that a neuropathic pain mouse with poor response to the Nav1.7 small-molecule inhibitor has better response to the Nav1.8 small-molecule inhibitor. According to the discovery, the analgesic effect of combined administration of different Nav1.7 inhibitors and Nav1.8 inhibitors is researched, and it is found that the analgesic effect can be remarkably improved and the response rate can be increased to 100% by combined administration of appropriate doses of the Nav1.7 inhibitor PF-05089771 and the Nav1.8 inhibitor PF-04885614. Therefore, the composition of the PF-05089771 and the PF-04885614 can be used for treating diseases caused by too high activity of the Nav1.7 or the Nav1.8, and the diseases include but are not limited to intractable pain and itching.

The present invention provides an antibody or antibody fragment thereof for a targeted cytomembrane voltage-gated sodium channel α subunit Nav1.9. The specific binding target is a S3-4 ring of a voltage sensor paddle of a domain II of the voltage-gated sodium channel α subunit. The antibody or antibody fragment thereof is able to inactivate a voltage sensor valve, to make sodium ions unable to enter nerve cells normally, thereby achieving the effect of treating and relieving pains.

The present invention relates to oligonucleotides (oligomers) that are complementary to voltage-gated sodium ion channel encoding nucleic acids, such as SCN9A, which encodes the voltage-gated sodium channel Nav1.7. The oligonucleotides of the invention are capable of inhibiting the expression of voltage-gated sodium ion channels, such as Nav1.7, and are useful in the prevention or the treatment ofpain.