Selective Inhibition of ERK2 for Persistent Inflammatory and Neuropathic Pain

Background & Unmet Need

• Neuropathic pain is caused by neural damage or disease that affects the somatosensory system (e.g., diabetic peripheral neuropathy)
• Inflammatory pain is caused by injury or disease-induced release of inflammatory mediators (e.g., rheumatoid arthritis)
• The extracellular signal-regulated kinase 1 (ERK1) and ERK2 are evolutionary conserved serine/threonine protein kinases
• ERK1/2 signaling in spinal cord dorsal horn (SCDH) has been implicated in injury-induced pain hypersensitivity
• Unmet Need: Novel therapeutic approaches for long-term, safe control of pain

Technology Overview

• The Technology: Methods and compositions for treating pain by administering a neurotropic recombinant adeno-associated virus (rAAV) encoding a nucleic acid inhibitor of ERK2 expression
• Discovery: Selective inhibition of ERK2 expression in neurons of the SCDH in mice with a small interfering RNA (siRNA) protects against pain
• PoC Data: The ERK2 siRNA protected mice against mechanical allodynia and thermal hypersensitivity following the induction of peripheral inflammation in the hind paw
• Findings demonstrate that ERK2 in SCDH neurons is critical for signaling the development of pain hypersensitivity and that ERK2 inhibition can reduce or inhibit pain transmission in the CNS

Technology Applications

• Treatment and prevention of neuropathic and inflammatory pain
• Research tool for siRNA inhibition of ERK2 to foster additional studies on the mechanisms of pain

Technology Advantages

• Unlike opioids, this approach is not associated with the development of tolerance, overdose, or abuse
• Delivery of the siRNA by an adeno-associated viral vector has the potential to deliver long-term pain relief