Selective Inhibition of ERK2 for Persistent Inflammatory and Neuropathic Pain
- *Abstract
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Inventions - siRNA molecules that selectively target Extracellular signal-Related Kinase 2 (ERK2)
- recombinant AAV2 vectors carrying the siRNA
- A method to treat persistent pain by selectively targeting ERK2
- A method to identify nonvector drugs that target ERK2
Research in the lab of Dr. Charles Inturrisi has shown that inhibition of ERK2 in the spinal cord dorsal horn can prevent injury-induced pain hypersensitivity. The lab proved this by using a recombinant AAV2 vector to deliver three different siRNA sequences against ERK2 to mice with persistent pain. Selective inhibition of ERK2 expression did not alter ERK1 expression or normal sensory responses but protected mice from developing injury-induced pain.
While the idea that ERK1/2 signaling in the spinal cord dorsal horn (SCDH) is important for injury-induced pain hypersensitivity is not new, the structural resemblance between ERK1 and ERK2, has limited the creation of selective inhibitors of either protein. The ERK2 knockout mouse is not viable, suggesting that systemic inhibition may not be a good option. Further, no one has been able to differentially target ERK2 in neurons as opposed to glial cells. Dr. Inturrisi's use of gene expression therapy to locally and selectively inhibit ERK2 activity in spinal cord neurons, is the first demonstration that ERK2 is a valid target for chronic pain.
Relevant indications include: chronic back pain and persistent pain associated with osteoarthritis, cancer pain and all forms of neuropathic pain. In the US, back pain alone costs 50 billion a year in health care expenditures. The world market for neuropathic pain management is projected to reach approximately $1.5 billion by 2010. Drug treatment of these persistent pain conditions is often limited by therapeutic failures and when opioids are used, by a concern for abuse. Our method represents a novel, targeted therapeutic approach without the concern for abuse liability.
- *Licensing
- Dan-Oscar Antsonda429@cornell.edu212-746-1297
- 其他
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Xu, Q., et al (2008). Activation of the neuronal extracellular signal-regulated kinase 2 (ERK2) in the spinal cord dorsal horn is required for CFA-induced pain hypersensitivity. J Neurosci. 28(52):14087-96.
- 国家/地区
- 美国
