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McGowan Institute for Regenerative Medicine affiliated faculty member Joseph Glorioso III, PhD, Co-founder, CODA Biotherapeutics, and Professor and Emeritus Chair, Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, is working on a gene therapy approach for treating chronic pain.  CODA is developing engineered neurotransmitter receptors that are activated exclusively by orally bioavailable drugs to control the activity of hyperexcitable neurons responsible for chronic neuropathic pain. The gene encoding the receptor is delivered to dysfunctional neurons by proprietary viral vectors that are optimized for robust and targeted gene transfer. Standard neurosurgical procedures are used to administer these viral vectors directly to the neurons to be controlled. Once expressed, the engineered receptor can be activated by the drug to modulate neuronal activity. This enables the selective, tunable and reversible regulation of the receptor – and hence cellular activity – based on the dosing regimen of the drug. CODA is engineering receptors to have exquisite sensitivity for the pharmacological activator, which should dramatically limit off-target side effects that plague many pharmaceutical treatments.

As reported by Megan Molteni for Wired, in 2014 Dr. Glorioso co-founded CODA Biotherapeutics to develop a gene therapy approach for treating chronic pain. Based in South San Francisco, CODA has so far raised $19 million to engineer receptors in people’s sensory neurons that can be controlled by a small molecule drug. The idea is to use a virus that evolved in nature to infiltrate the hyperexcitable nerves responsible for many kinds of neuropathic pain—from arthritic joints to thrown-out backs and nerve damage caused by many cancer treatments. A one-time injection into the skin sends the virus into the nerve cells, delivering the instructions for making this tunable on/off switch. When a patient feels pain, they take the drug, which cuts the power to the neurons’ electrical activity and shuts down the perception of pain, with minimal body-wide side effects and risks of addiction. Dr. Glorioso expects it will be 18 to 24 months before an experimental therapy is ready to test in humans. CODA is starting first with types of pain so severe they’re basically untreatable, but the same approach could also be applied to other neurological conditions, including anxiety, Dr. Glorioso says.

More than 19 million Americans live with chronic neuropathic pain. Nearly 10 million Americans take opioids for long-term pain and 2.1 million are estimated by the National Institutes of Health to be addicted. Current pharmacological therapies such as opioids, anticonvulsants, tricyclic anti-depressants and channel inhibitors provide little relief while having significant side effects and a potential for addiction. Nerve stimulation therapies require batteries and wires that need maintenance and carry a risk of infections. Surgeries that destroy pathological neurons are a last resort and can have permanent adverse effects on peripheral nervous system function.