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Alpha4Beta2 Nicotinic Agonist for Treatment of L-Dopa Refractory Gait and Balance Disorders in Parkinson Disease

Study Rationale:
Gait and balance problems, particularly falls, are common and disabling symptoms in Parkinson disease (PD), and do not improve markedly with existing treatments. Studies have indicated that loss of the brain chemical messenger acetylcholine causes gait and balance problems in PD. A widely used FDA-approved drug, varenicline, mimics some of the important actions of acetylcholine. Using a combination of modern imaging methods and laboratory measures of gait and balance, we will determine whether varenicline improves the control of gait and balance in individuals with PD.

Hypothesis:
Varenicline will improve gait speed and improve balance in Parkinson's disease.  

Study Design:
This study has two phases. In the first phase, we will use an neuroimaging method called positron emission tomography and gradually increase levels of varenicline to find the most appropriate dose. In the second phase, we will administer the selected dose of varenicline to Parkinson's disease participants in a double-blind crossover trial. Laboratory measures of gait and balance will be obtained when participants are on and off varenicline, allowing us to determine if varenicline, or similar drugs, should be pursued as treatments for Parkinson's disease.

Impact on Diagnosis/Treatment of Parkinson's Disease:
We hope to identify a drug that may be useful in reducing falls in Parkinson's patients. 

Next Steps for Development:
If successful, we will conduct a larger study addressing the safety of varenicline in a broader population of Parkinson’s disease patients. Subsequently, we would pursue a large clinical trial to determine if varenicline reduces falls in Parkinson's disease.


Researchers

  • Roger L. Albin, MD

    Ann Arbor, MI United States


  • William T. Dauer, MD

    Ann Arbor, MI United States


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