University of Pittsburgh researchers have developed a potential treatment for peripheral persistent pain. Using a herpes simplex virus (HSV) vector (vHGlyRα1), the genetic code for the human alpha1 subunit of the glycine receptor (GlyR) can be delivered to neuronal cells lacking endogenous GlyR. Increasing GlyR levels and administration of glycine can silence these neurons and could be a novel therapeutic approach to managing chronic pain conditions.
Description
Persistent pain is a significant health burden globally with nearly half of all chronic pain patients finding little or no relief from existing treatments. In the central nervous system (CNS) of adults, GlyR can silence neurons through the regulation of electrical activity (Cl-currents) in cells. GlyR is only expressed in the spinal cord and lower brain, not neurons in the periphery. This novel treatment results in GlyR expression in peripheral neurons following infection with a HSV vector vHGlyRα1 and can reduce pain responses in animals. This therapeutic strategy to treat chronic neuropathic pain in a targeted manner, without the risk of addiction or other adverse effects has the potential to revolutionize pain management and improve the lives of patients.
Applications
- Chronic pain
- Neuropathic pain
Advantages
Chronic pain is a major cause of human suffering, affecting the quality of life of millions with a substantial financial impact due to associated healthcare costs and loss of productivity. Pain-related pathways are complex, making selective targeting of their root cause, particularly when peripheral neurons are involved, difficult. These complexities have led to systemic treatment of pain which can lead to tolerance, addiction, and other side effects including delirium, gastrointestinal issues, and nausea.
Central neurons in the HSV-based vectors have previously been found to infect primary sensory neurons. GlyR is a member of the nicotinicoid superfamily of ligand-gated ionotropic receptors that can modulate neurotransmission. The α1-subunit of GlyR alone can replicate the ligand-gated properties of GlyR. Using HSV-based vectors it is possible to infect neuronal cells and deliver the cDNA encoding for the α1-subunit of GlyR, leading to its expression and subsequent alleviation of pain following application of glycine. This approach allows for treatment of previously unmanageable peripheral nerve pain.
Invention Readiness
In vitro results have confirmed that inoculation with vHGlyRα1 leads to expression of the α1-subunit of GlyR in DRG cells. In vivo studies using intradermal delivery of vHGlyRα1 allowed for control of pain response using GlyR agonists or antagonists. Pain responses could be further optimized via mutagenesis and/or application of agonists, antagonists or other agents.
IP Status
https://patents.google.com/patent/US11725038B2
