Laura Cavallone, MD
Cavallone joined the Department of Anesthesiology at Washington University in St. Louis in 2004. Since then she has been actively involved in basic science and translational investigations focusing on mechanisms of central sensitization, under the mentorship and guidance of Dr. Robert W. Gereau IV, Ph.D.
Working in collaboration with Gereau, Cavallone’s specific interest has been the role of the G-protein coupled metabotropic glutamate receptor 5 (mGlu5) in the modulation of mechanisms of central sensitization and development of chronic pain syndromes.
The G-protein coupled metabotropic glutamate receptor 5 (mGlu5) is expressed at synapses throughout the nervous system, in particular the pain neuraxis, and agents that modulate mGlu5 may have therapeutic potential in the treatment of pain. Significant advancements into the use of pharmacologic agents acting at mGlu receptors in human patients have been made recently, and pre-clinical findings that activation of mGlu5 is pro-nociceptive whereas its inhibition is anti-nociceptive have led to the suggestion that antagonism of mGlu5 may have analgesic efficacy in humans.
In a series of studies in mice conducted by Gereau’s group, the experimental drug fenobam, an antagonist for the mGlu5, has been shown to produce acute analgesia in rodents, and mice treated with fenobam did not develop tolerance (J Pharmacol Exp Ther. 2009 Sep;330(3):834-43; Anesthesiology. 2011 Dec;115(6):1239-1250).
Founded on her basic science knowledge, her experience with experimental animal models and her clinical background, Cavallone’s role has evolved into spearheading a translational research project aimed at reproducing in human subjects the promising pre-clinical results obtained in mice.
In search for a suitable model to test the potential for development of fenobam and other mGlu5 antagonists for clinical use as analgesics, Cavallone has investigated human experimental pain models of hyperalgesia. She is now working at characterizing the pharmacokinetics of fenobam after oral administration, and testing the anti-hyperalgesiac efficacy of fenobam in the heat/capsaicin sensitization model applied to healthy volunteers.
Of note, fenobam is not currently available on the market, and all of the studies involving use of fenobam are covered by an IND that Cavallone is currently holding with the FDA as PI and Sponsor.