An all-optical electrophysiology platform for the discovery of pain therapeutics

Information

  • Research Project
  • 9558625
  • ApplicationId
    9558625
  • Core Project Number
    R44NS107041
  • Full Project Number
    1R44NS107041-01
  • Serial Number
    107041
  • FOA Number
    PA-17-302
  • Sub Project Id
  • Project Start Date
    7/1/2018 - 6 years ago
  • Project End Date
    6/30/2019 - 5 years ago
  • Program Officer Name
    FERTIG, STEPHANIE
  • Budget Start Date
    7/1/2018 - 6 years ago
  • Budget End Date
    6/30/2019 - 5 years ago
  • Fiscal Year
    2018
  • Support Year
    01
  • Suffix
  • Award Notice Date
    6/20/2018 - 6 years ago

An all-optical electrophysiology platform for the discovery of pain therapeutics

Project Summary Chronic pain affects over 100 million adults in the United States and is challenging to treat. Current treatments include opioids and non-steroidal inflammatory agents. However, efficacy of these drugs in chronic treatment is restricted by dose limiting toxicities, and prolonged opioid use can lead to dependency. Despite the clear, unmet medical need and significant research activity, few drugs targeting pain based on novel, non-opioid mechanisms have appeared in the past decade. Q-state has created a novel all-optical platform (Optopatch) using engineered optogenetic proteins and custom microscopes to simultaneously stimulate and record electrical activity from a variety of cell types with high sensitivity and temporal resolution. We focus our efforts on a genetically validated pain target, SCN9A (Nav1.7), a voltage-gated sodium channel that is required for pain signal transmission in sensory neurons. We will apply Optopatch technology in two formats. 1) An HTS screen of the Q-State chemical library using a heterologously expressed Nav1.7 channel assay that replicates physiological spiking activity. Counterscreens against other Nav1.x channels will be performed in the same assay format to determine compound selectivity. 2) Identified inhibitors will be evaluated in medium throughput screens that measure excitability in rodent sensory and human iPS sensory neurons that have been sensitized using inflammatory mediators. This integrated set of assays is designed to identify Nav1.7 inhibitors acting by diverse working mechanisms and prioritize compounds for further optimization using scalable in vitro models of sensory neuron function. This platform will be employed as an efficient means to select compounds for optimization using medicinal chemistry and pharmacokinetic, drug metabolism and in vivo efficacy data.

IC Name
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
  • Activity
    R44
  • Administering IC
    NS
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    222370
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    853
  • Ed Inst. Type
  • Funding ICs
    NINDS:222370\
  • Funding Mechanism
    SBIR-STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    Q-STATE BIOSCIENCES, INC.
  • Organization Department
  • Organization DUNS
    078880703
  • Organization City
    CAMBRIDGE
  • Organization State
    MA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    021394238
  • Organization District
    UNITED STATES