Targeted Gene Therapies for Pain and Neuro-Related Disorders

University of Pittsburgh researchers have developed a novel gene therapy targeting specific subsets of neurons involved in persistent pain, including inflammatory and neuropathic pain. The therapy leverages a designer receptor activated by synthetic ligands, which can effectively block neural signaling in cells that express specific markers like CCK, PKCgamma, or calretinin. The innovative approach promises to provide long-lasting relief from chronic pain conditions without the side effects commonly associated with opioid-based treatments.

A designer receptor (PSAM-GlyR) was used to identify specific subsets of dorsal horn neurons involved in persistent pain sensation. The figure illustrates the injection of the PSAM-GlyR receptor, delivered via AAV, into the dorsal horn. When the ligand is applied to a PSAM-GlyR-expressing cell, it induces hyperpolarization and inhibits action potentials, confirming its ability to block action potential-dependent neurotransmitter release.

Description

The targeted gene therapies utilize a specially designed receptor that can be activated by specific synthetic ligands to disrupt neuronal signaling in subsets of neurons expressing cholecystokinin (CCK), PKCgamma, or calretinin. These receptors are delivered via viral vectors to the spinal cord dorsal horn, where they block persistent pain signals. The therapy is administered through an injection, with effects lasting 5-10 years, and the synthetic ligand is taken orally.

Applications

- Treatment of persistent pain (inflammatory and neuropathic pain)
- Chronic pain management
- Neuro-related disorder treatments
- Research in neural signaling and pain pathways

Advantages

The therapy offers highly specific targeting of pain-related neurons, resulting in long-lasting effects with a single injection and a reduced risk of side effects compared to current pain therapies. This specificity and longevity make it a promising alternative to opioid-based painkillers, potentially addressing the opioid crisis by providing a safer and more effective pain management solution.

Invention Readiness

The therapy is in the development stage, with data showing efficacy in rodent models. Experimental results indicate that versions of these therapies alleviate persistent mechanical and thermal pain in rodents without affecting motor function or acute somatosensation.

IP Status

https://patents.google.com/patent/US20230323402A1