Abstract: The present invention features novel peripherally-restricted non-benzodiazipene analogs with reduced blood brain barrier permeability and methods of use thereof for reducing tactile dysfunction, social impairment, and anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett syndrome, Phelan McDermid syndrome, or Fragile X syndrome, or for treating touch over-reactivity, pain, or mechanical allodynia.

Abstract: The present invention features a method of reducing tactile dysfunction or anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett Syndrome, or Fragile X syndrome by administering a GABAA agent having reduced blood brain barrier or by expressing a nucleic acid encoding an exogenous alpha or beta subunit of a GABAA receptor in dorsal root ganglion neurons in the subject using a vector.

Abstract: The present invention features a method of reducing tactile dysfunction or anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett Syndrome, or Fragile X syndrome by administering a GABAA agent having reduced blood brain barrier or by expressing a nucleic acid encoding an exogenous alpha or beta subunit of a GABAA receptor in dorsal root ganglion neurons in the subject using a vector.

Abstract: The present invention features novel peripherally-restricted non-benzodiazipene analogs with reduced blood brain barrier permeability and methods of use thereof for reducing tactile dysfunction, social impairment, and anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett syndrome, Phelan McDermid syndrome, or Fragile X syndrome, or for treating touch over-reactivity, pain, or mechanical allodynia.

Abstract: In some aspects, the disclosure relates to a prepulse inhibition (PPI) assay comprising the steps of, administering a tactile prepulse to a human subject, administering a startle stimulus to the subject, and measuring the subject's response to the startle stimulus. In another aspect, the disclosure relates to a method for evaluating tactile hypersensitivity and/or sensorimotor impairment in a human subject, comprising, administering to the subject a PPI assay according to any one of the preceding claims, comparing the assay results to neuro-typical controls, and determining the degree of tactile hypersensitivity and/or sensorimotor impairment in the subject.

Abstract: The present invention provides novel peripherally-restricted benzodiazepines with reduced blood brain barrier permeability and methods of use thereof for reducing tactile dysfunction, social impairment, and anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett syndrome, Phelan McDermid syndrome, or Fragile X syndrome.

Abstract: The present disclosure provides a newly conceived of platform for identifying novel pain and/or pruritus-inhibiting agents (e.g., small molecule compounds, peptides, antigen binding proteins (e.g., antibodies or antibody fragments) that are efficacious, safe, and non-addictive alternatives for pain and pruritus management in place of (or in some embodiments, in combination with) “first line” treatments, such as gabapentin, pregabalin, and opioids. The present disclosure also provides for a method of treating pain and/or a pruritus comprising administering a therapeutically effective amount of an agent that activates a Gai/o-coupled G-Protein Coupled Receptor (GPCR) that is selectively expressed in the nociceptor and/or pruriceptor neuron subtypes of the somatosensory neurons.

Abstract: The present invention features novel peripherally-restricted non-benzodiazipene analogs with reduced blood brain barrier permeability and methods of use thereof for reducing tactile dysfunction, social impairment, and anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett syndrome, Phelan McDermid syndrome, or Fragile X syndrome, or for treating touch over-reactivity, pain, or mechanical allodynia.

Abstract: The present invention features novel peripherally-restricted isoguvacine analogs with reduced blood brain barrier permeability and methods of use thereof for reducing tactile dysfunction, social impairment, and anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett syndrome, Phelan McDermid syndrome, or Fragile X syndrome.

Abstract: The present invention features a method of reducing tactile dysfunction or anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett Syndrome, or Fragile X syndrome by administering a GABAA agent having reduced blood brain barrier or by expressing a nucleic acid encoding an exogenous alpha or beta subunit of a GABAA receptor in dorsal root ganglion neurons in the subject using a vector.

Abstract: The semaphorin family contains a large number of plylogenetically conserved proteins and includes several members that have been shown to function in repulsive axon guidance. Semaplorin III (Sema III) is a secreted protein that in vitro causes neuronal growth cone collapse and chemorepulsion of neurites, and is required in vivo for correct sensory afferent innervation and other aspects of development. The mechanism of Sema III function, however, is unknown. Here, we report that neuropilin, a type I transmembrane protein, is a Sema III receptor. We also describe the identification of neuropiln-2, a related neuropilin family member, and show that neuropilin and neuropilin-2 are expressed in overlapping, yet distinct, populations of neurons in the rat embryonic nervous system.