GABA-A, a New Avenue in PD Research

Nicolaas Bohnen, MD, PhD
Director, University of Michigan, Functional Neuroimaging, Cognitive and Mobility Laboratory at Domino’s Farms in
Ann Arbor:

Our research group has a long-standing interest in studying symptoms of Parkinson’s disease (PD) that may not respond well to dopaminergic medications, such as carbidopalevodopa (Sinemet). These features include difficulties with balance and walking like falls and freezing of gait, daytime excessive sleepiness and memory and thinking problems. While the chemical messenger molecule, dopamine, has been extensively studied in PD, we are looking at other chemical messenger molecules that may change in the brain in people with PD, such as acetylcholine and GABA.

Animal studies of PD suggest that one of the reasons why people with PD have difficulties with balance and gait is that GABA is excessively blocking the outgoing connections of the basal ganglia (movement centers) in the brain. Therefore, the use of medications that may slightly decrease these excessive blocking functions may help people with PD to
move better. Our lab is looking at drugs that are already approved by the FDA for other indications that may calm
down the excessive GABA blocking functions in the brain. One of these medications is flumazenil. Flumazenil is a drug
that is given as a small injection in a vein. Interestingly, previous studies with flumazenil in people with PD have
shown that it improves motor functions, such as the speed of finger tapping. We are looking to see if it may improve balance and walking functions. The study also will involve brain MRI and PET imaging studies. The PET studies will look at the amount of dopamine and GABA in the brain.

Research with PD or other subjects should always begin with an initial discussion of the particular study and obtaining the
participant’s written informed consent. In our PD studies, a detailed history of patient’s PD and other medical problems follows, as well as several assessments, including: a PDspecific neurologic exam called the Movement Disorder
Society-United Parkinson Disease Rating Scale (MDS-UPDRS), sensored measurements of gait and balance, fine motor tests, and PD-related testing on memory and thinking. In addition to investigating GABA-A receptors with flumazenil, our lab is immersed in other research studies for subjects with PD. We also have research interests in dementia with Lewy bodies, also called DLB.

While there is no guarantee that a research study will directly help someone’s condition, participating in research may help others by advancing medical knowledge. Participants usually learn a little more about their own disease through research studies. Our staff is caring and committed to excellence; many of our subjects return to participate in more studies.

If you or someone you know with PD is interested in becoming a clinical research subject, please contact our Functional Neuroimaging, Cognitive & Mobility Laboratory at pdresearch@med.umich.edu or at 734-998-8400 (toll-free 877-998-1098). Information about our lab can be found at pdresearch.rad.umich.edu. A comprehensive description of university-wide studies can also be found at UMHealthresearch.org.