Effect of odorant on mortality and extended amygdala activation in Dravet syndrome

William Nobis MD, PHD

William Nobis, MD, PhD – Vanderbilt University
Effect of odorant on mortality and extended amygdala activation in Dravet syndrome
Research Grant – 2 years, $165,000
**Co-funded with JAM for Dravet

Grant Summary:
 Dravet syndrome (DS) is associated with a high epilepsy-related mortality, including an increased risk of sudden unexpected death in epilepsy (SUDEP). Controlling seizures can decrease the risk of SUDEP, but seizures in DS are often refractory and anti-seizure medications have unwanted side effects, outlining the need for a benign treatment option to modify mortality risk. Odor therapy, or aromatherapy, has been used for a therapy for stress, depression and neurologic disease including a historical background in treating seizures. The olfactory system is unique in that it is a sensory organ that does not send its information to the thalamus, rather it has direct connections to olfactory areas of the brain but also to areas that are more evolutionarily and classically involved in stress, fear, threat detection and social functioning. These include areas of the brain known collectively as the extended amygdala. More recent work by myself and others have determined that there is a role of these amygdalar circuits in control of respirations and potentially seizure related breathing dysfunction. Odorants that have a direct input to amygdalar circuits have the potential to modulate these circuits and may provide a non-invasive, well-tolerated means to decrease seizure-related death by preventing activation of these regions and altering seizure-related breathing dysfunction. Our hypothesis is that chronic exposure to the odorant 2-phenylethanol (“rose odor”) will decrease mortality and improve neuropsychiatric comorbidities of DS through attenuation of extended amygdalar neuronal activation. Exciting preliminary data using a mouse model of DS suggests that mortality is significantly reduced by chronic exposure to this odor, our goal is to build on this data to better explore the effects of odor exposure on mortality, seizure frequency and neuropsychiatric comorbidities. This work would provide scientific rationale for the use of odor therapy to manage symptoms of epilepsy and DS, this would be immediately clinically impactful and could readily be evaluated in clinical setting to prove efficacy in human patients. 

About the Investigator: Dr. William Nobis is an Assistant Professor at Vanderbilt University Medical Center. He completed the Medical Scientist Training Program at Vanderbilt University in 2011 where he earned both his M.D. and a Ph.D. in Neuroscience followed by Neurology and Epilepsy training at Northwestern University in Chicago, where he served as chief resident in 2015. Dr. Nobis’ research focuses on sudden unexpected death in epilepsy (SUDEP), in particular electrophysiological and targeted functional anatomical evaluation of extended amygdalar circuits and its relation to seizures and respiratory control in genetic epilepsies such as Dravet syndrome.

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