Abstract: A non-human animal model for neurodegenerative and/or inflammatory diseases is provided, which non-human animal comprises a disruption in a C9ORF72 locus. In particular, non-human animals described herein comprise a deletion of an entire coding sequence of a C9ORF72 locus. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)), autoimmune and/or inflammatory diseases (e.g., SLE, glomerulonephritis) are also provided.

Abstract: The present invention provides antibodies and antigen-binding fragments thereof that specifically bind to cells expressing acid-sensing ion channel-1 (ASIC1). According to certain embodiments of the invention, the antibodies inhibit acid-induced, ASIC1-mediated ion currents in cells expressing human ASIC1. The antibodies of the invention are useful for the treatment of pain, including pain associated with surgical intervention and various diseases and disorders.

Abstract: A non-human animal model for neurodegenerative and/or inflammatory diseases is provided, which non-human animal comprises a disruption in a C9ORF72 locus. In particular, non-human animals described herein comprise a deletion of an entire coding sequence of a C9ORF72 locus. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)), autoimmune and/or inflammatory diseases (e.g., SLE, glomerulonephritis) are also provided.

Abstract: A non-human animal model for neurodegenerative and/or inflammatory diseases is provided, which non-human animal comprises a disruption in a C9ORF72 locus. In particular, non-human animals described herein comprise a deletion of an entire coding sequence of a C9ORF72 locus. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)), autoimmune and/or inflammatory diseases (e.g., SLE, glomerulonephritis) are also provided.

Abstract: The present invention provides antibodies and antigen-binding fragments thereof that specifically bind to cells expressing acid-sensing ion channel-1 (ASIC1). According to certain embodiments of the invention, the antibodies inhibit acid-induced, ASIC1-mediated ion currents in cells expressing human ASIC1. The antibodies of the invention are useful for the treatment of pain, including pain associated with surgical intervention and various diseases and disorders.

Abstract: The present invention provides antibodies that bind to prokineticin receptors (PROKRs) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human PROKR1 and/or PROKR2. The present invention includes antibodies that bind cell surface-expressed PROKR1 and/or PROKR2. In certain embodiments, the antibodies of the present invention are capable of blocking prokineticin (PK)-mediated activation of one or more PROKR. The antibodies of the invention are useful for the treatment of various diseases and disorders mediated by prokineticin signaling.

Abstract: The present invention provides antibodies that bind to prokineticin receptors (PROKRs) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human PROKR1 and/or PROKR2. The present invention includes antibodies that bind cell surface-expressed PROKR1 and/or PROKR2. In certain embodiments, the antibodies of the present invention are capable of blocking prokineticin (PK)-mediated activation of one or more PROKR. The antibodies of the invention are useful for the treatment of various diseases and disorders mediated by prokineticin signaling.

Abstract: A non-human animal model for neurodegenerative and/or inflammatory diseases is provided, which non-human animal comprises a disruption in a C9ORF72 locus. In particular, non-human animals described herein comprise a deletion of an entire coding sequence of a C9ORF72 locus. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)), autoimmune and/or inflammatory diseases (e.g., SLE, glomerulonephritis) are also provided.

Abstract: The present invention provides antibodies and antigen-binding fragments thereof that specifically bind to cells expressing acid-sensing ion channel-1 (ASIC1). According to certain embodiments of the invention, the antibodies inhibit acid-induced, ASIC1-mediated ion currents in cells expressing human ASIC1. According to certain embodiments, the antibodies of the invention are selective for ASIC1 and do not bind other acid-sensing ion channels in the absence of ASIC1. The antibodies of the invention are useful for the treatment of pain, including pain associated with surgical intervention and various diseases and disorders.

Abstract: The present invention provides antibodies and antigen-binding fragments thereof that specifically bind to cells expressing acid-sensing ion channel-1 (ASIC1). According to certain embodiments of the invention, the antibodies inhibit acid-induced, ASIC1-mediated ion currents in cells expressing human ASIC1. The antibodies of the invention are useful for the treatment of pain, including pain associated with surgical intervention and various diseases and disorders.

Abstract: The present invention provides antibodies and antigen-binding fragments thereof that specifically bind to cells expressing acid-sensing ion channel-1 (ASIC1). According to certain embodiments of the invention, the antibodies inhibit acid-induced, ASIC1-mediated ion currents in cells expressing human ASIC1. The antibodies of the invention are useful for the treatment of pain, including pain associated with surgical intervention and various diseases and disorders.

Abstract: The present invention provides antibodies that bind to prokineticin receptors (PROKRs) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human PROKR1 and/or PROKR2. The present invention includes antibodies that bind cell surface-expressed PROKR1 and/or PROKR2. In certain embodiments, the antibodies of the present invention are capable of blocking prokineticin (PK)-mediated activation of one or more PROKR. The antibodies of the invention are useful for the treatment of various diseases and disorders mediated by prokineticin signaling.

Abstract: The present invention provides antibodies that bind to protease-activated receptor-2 (PAR-2) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human PAR-2. The antibodies of the invention are useful, inter alia, for the treatment of diseases and disorders associated with one or more PAR-2 biological activities, including the treatment of pain conditions, inflammatory conditions and gastrointestinal conditions.

Abstract: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a humanization of an extracellular loop of an endogenous NaV channel gene, in particular a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein. Genetically modified non-human animals are also provided, wherein the genetic modification comprises replacement of an endogenous NaV channel gene, in particular a replacement of the endogenous NaV1.7 gene with a human NaV1.7 gene, and wherein the genetically modified non-human animals are capable of generating action potentials and communicating through the excitable cells of the genetically modified non-human animals via the expressed human or humanized NaV1.7 protein the surface of the excitable cells. Genetically modified mice are described, including mice that express the human or humanized NaV1.7 gene from the endogenous NaV1.

Abstract: The present invention provides antibodies that bind to prokineticin receptors (PROKRs) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human PROKR1 and/or PROKR2. The present invention includes antibodies that bind cell surface-expressed PROKR1 and/or PROKR2. In certain embodiments, the antibodies of the present invention are capable of blocking prokineticin (PK)-mediated activation of one or more PROKR. The antibodies of the invention are useful for the treatment of various diseases and disorders mediated by prokineticin signaling.

Abstract: The present invention provides antibodies and antigen-binding fragments thereof that specifically bind to cells expressing acid-sensing ion channel-1 (ASIC1). According to certain embodiments of the invention, the antibodies inhibit acid-induced, ASIC1-mediated ion currents in cells expressing human ASIC1. According to certain embodiments, the antibodies of the invention are selective for ASIC1 and do not bind other acid-sensing ion channels in the absence of ASIC1. The antibodies of the invention are useful for the treatment of pain, including pain associated with surgical intervention and various diseases and disorders.

Abstract: Methods and compositions for using genetically modified non-human animals are provided, wherein the genetic modification comprises a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein or a complete humanization of an endogenous NaV1.7 gene. Methods for using isolated DRG cultures from genetically modified non-human animals are also provided, wherein the isolated DRG express a human or chimeric NaV1.7 protein on the surface, in particular measuring primary nociceptive activation through the release of calcitonin gene-related peptide (CGRP) in isolated DRG in vitro, and wherein the isolated DRG cultures are capable of generating action potentials and communicating through an excitable signal via the expressed human or chimeric NaV1.7 protein the cell surface. In vivo and in vitro methods for characterizing NaV1.7-specific antagonists and evaluation of corresponding therapeutic potential for NaV1.7-mediated disease are also provided.

Abstract: The present invention provides methods for treating pruritus by blocking human protease activated receptor-2 (PAR2) activity. The methods of the invention can be used to treat pruritus associated with atopic dermatitis, psoriasis, burn scarring, hypertrophic scarring, keloids, renal failure or hepatic failure. The methods of the invention include administering an antibody or antigen-binding fragment thereof that specifically binds human PAR2.

Abstract: The present invention provides methods for treating pruritus by blocking human protease activated receptor-2 (PAR2) activity. The methods of the invention can be used to treat pruritus associated with atopic dermatitis, psoriasis, burn scarring, hypertrophic scarring, keloids, renal failure or hepatic failure. The methods of the invention include administering an antibody or antigen-binding fragment thereof that specifically binds human PAR2.

Abstract: Methods and compositions for using genetically modified non-human animals are provided, wherein the genetic modification comprises a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein or a complete humanization of an endogenous NaV1.7 gene. Methods for using isolated DRG cultures from genetically modified non-human animals are also provided, wherein the isolated DRG express a human or chimeric NaV1.7 protein on the surface, in particular measuring primary nociceptive activation through the release of calcitonin gene-related peptide (CGRP) in isolated DRG in vitro, and wherein the isolated DRG cultures are capable of generating action potentials and communicating through an excitable signal via the expressed human or chimeric NaV1.7 protein the cell surface. In vivo and in vitro methods for characterizing NaV1.7-specific antagonists and evaluation of corresponding therapeutic potential for NaV1.7-mediated disease are also provided.