Novel opsins for optogenetic-based analgesia

Project Overview

Chronic pain —pain lasting months or years— affects one in five Canadians, reducing quality of life and burdening the healthcare system. Current treatments, including opioids, anti-inflammatory drugs, and nerve blocks, work imprecisely, affecting the entire nervous system and causing significant side effects. A fundamentally better approach would silence only the specific nerve cells that carry pain signals, leaving other sensations and functions intact.
Optogenetics is a technique that makes targeted nerve cells sensitive to light, allowing them to be switched off precisely and reversibly with a flash of illumination. Until now, clinical application of optogenetics for pain has been blocked by three problems: light cannot easily reach deep nerves through skin and tissue; the most common light-activated silencing tools stop working in the diseased nerve state they are supposed to treat; and keeping nerves silenced requires continuous light, which can damage tissue.
This project exploits a new generation of light-sensitive proteins —called optoGPCRs— that solve all three problems at once. They are exquisitely sensitive to light, activatable through skin with safe low-power illumination; they silence nerves through a mechanism that remains fully effective even in diseased tissue; and a single brief flash produces minutes of sustained silencing, eliminating the need for continuous light.
We will deliver these proteins to pain-carrying nerve cells using engineered viruses injected into the bloodstream, guided to the spine by focused ultrasound that temporarily opens the spinal barrier. We will first validate the approach in mice, then demonstrate it in pigs— whose spine closely resembles the human spine— measuring pain relief by brain imaging. We will also develop virus variants that do not require genetic modification of the patient, an essential step toward clinical use.
All tools developed will be shared freely with the research community, accelerating the path from laboratory discovery to patient benefit.

Partners and Donors

Brain Canada, Weizmann Canada, and the Weizmann Institute of Science