Brainstem and Olfactory System Biomarkers of Early Parkinson's Disease
Improved Biomarkers and Clinical Outcome Measures, 2016
There is a great need to identify Parkinson's disease (PD) in its earliest stages when interventions may prevent or slow neural degeneration. Given that the earliest brain pathology of PD occurs outside of the motor system, namely in the olfactory bulbs (brain regions that detect smell) and the brainstem (brain region that controls involuntary functions), we are probing the function of these regions using sensory and physiological tests in healthy persons and in those with PD, Alzheimer's disease and other disorders. We have discovered a novel and robust electrophysiological (electrical signaling) brainstem response that appears to be more sensitive and specific in differentiating those with PD from healthy individuals and from individuals with other neurological disorders. This biomarker (tracks disease activity) response and its comparison to the gold standard of olfactory testing is the focus of this project.
We hypothesize that our novel brainstem response, termed the nasotrigeminal response, will clearly differentiate those with PD from healthy individuals and from those with Alzheimer's disease with 100% accuracy, be more specific than olfactory testing, be present in all those with PD and absent in all those with AD and healthy individuals and be decreased by light deprivation known to enhance the brain neurotransmitter (chemical messenger) GABA.
We will apply brief, mild electrical signals to selected sensory (touch) nerves on the face and record responses from muscles near the eye before and after brief periods of light deprivation (participants will wear opaque goggles). We will also administer a battery of olfactory tests and will compare the magnitude (amplitude) of the electrically-induced motor response to the olfactory test scores.
Impact on Diagnosis/Treatment of Parkinson's Disease:
The proposed research has the potential to revolutionize our understanding of brainstem pathology and has a strong likelihood of providing a sensitive and specific non-invasive biomarker for early stage PD. If successful, it will have significant consequences for clinical trials attempting to find drugs that eliminate or delay disease progression. This study also has the potential to produce a paradigm shift in PD research toward pathology within the brainstem, which has been largely overlooked. The electrical response is easily measured using traditional equipment found in most neurology clinics, making it a practical, inexpensive and non-invasive diagnostic measure.
Next Steps for Development:
There several subsequent steps that will make the results of this study applicable to the clinic. First, the application of the brainstem response measure beyond the neurological diseases studied will establish the breadth of its clinical utility in diagnosis. Second, longitudinal studies of at-risk individuals will determine its sensitivity in detecting PD during its early non-symptomatic, pre-symptomatic or pre-clinical period.
Professor of Otolaryngology: Head and Neck Surgery at University of Pennsylvania School of Medicine
Senior Research Investigator, Perelman School of Medicine at University of Pennsylvania
Location: Philadelphia, Pennsylvania, United States