Selective actin remodeling of sensory neurons for acute pain management
There is an urgent need for new approaches to treat acute human pain without the risks of Substance Use Disorders (SUDs).
The goal of Neurocarrus’ project is to obtain proof of concept for the use of a new non-addictive pain therapeutic to treat acute pain. When inflammation occurs, actin polymerization occurs in sensory neurons, leading to sensitization of purinergic receptors and abnormal pain behaviors. This process can be reversed by local injection of small molecule actin inhibitors that cause depolymerization. However, because they are untargeted, they have toxic profiles including diffuse cytotoxicity and fail as pain therapeutics. In this context, there is an unmet need for a product that can quickly and specifically disrupt peripheral sensory neurons to guarantee safe management of acute pain.
To prevent the off-target effects and to avoid actions affecting the central nervous system and muscle function, a sensory neuron-targeted actin depolymerizing agent called N-001 was developed. In vivo, N-001 administration by subcutaneous injection prevents pain in an acute pain rodent model at lower doses and with longer duration than achieved by opiates. In vitro, N-001 selectively targets sensory neurons and only after receptor mediated uptake, delivers an actin depolymerizing agent that alters neural conductivity in a reversible fashion. Further advancement of N-001 as a therapeutic candidate for acute pain requires demonstration of the feasibility of using N-001 as a product for human pain management.