Gift Will Aid Research Into Rare Brain Disorder

CINCINNATI—A $100,000 gift will enable a University of Cincinnati (UC) researcher to study a rare brain disorder that causes progressive problems with control of gait and balance and problems controlling eye movement.

Sheila Fleming, PhD, a researcher in the Gardner Center for Parkinson’s Disease and Movement Disorders at the UC Neuroscience Institute, will study progressive supranuclear palsy (PSP) with the aid of a very generous gift from Mrs. Caleb C. Whitaker III in honor of her late husband, who had the disease. 

PSP, whose motor symptoms may be confused with those of Parkinson’s disease, was first recognized as a distinct disorder in 1964, according to the National Institute of Neurological Disorders and Stroke (NINDS). Like Parkinson’s, its symptoms are caused by a gradual deterioration of brain cells in a few specific areas in the brain. 

Both PSP and Parkinson’s are characterized by movement difficulties. However, problems with speech and swallowing are much more common and severe in PSP than in Parkinson’s. Tremor, common in Parkinson’s, is rare in PSP. Eye movements are abnormal in PSP (patients report an inability to aim the eyes properly) but close to normal in Parkinson’s. 

Approximately 20,000 Americans have PSP, NINDS states, making it much less common than Parkinson’s. Affected individuals are usually middle-aged or elderly, and men are affected more often than women.

There is currently no effective treatment for PSP, according to NINDS. While Parkinson’s patients benefit from the drug levodopa, people with PSP respond poorly to it.

"Mrs. Whitaker’s generosity is inspiring,” says Rodney Grabowski, UC Foundation president. "Her gift will enable UC researchers to conduct studies that will potentially change the lives of thousands of patients and their families.”

Alberto Espay, MD, a movement disorders neurologist and clinical researcher in the department of neurology and rehabilitation medicine, recognized that Fleming’s particular expertise in genetic models of Parkinson’s disease could be applied to other forms of Parkinsonism such as PSP. He organized a brainstorming session with Irene Litvan, MD, at the International Parkinson and Movement Disorders Society’s 18th International Congress of Parkinson’s Disease and Movement Disorders in Stockholm. Litvan, of the University of California, San Diego, School of Medicine, is one of the world’s foremost authorities on PSP and a prolific author on the disorder. 

With Litvan’s input, Fleming proposes to develop a novel mouse model of PSP that recapitulates both brain pathology and behavioral dysfunction observed in PSP in humans and that can be utilized in preclinical trials testing potential therapeutics. Researchers will use fruit extracts from the pawpaw tree, which have been shown to be toxic to cortical neurons, in their efforts to model PSP in vivo.  

"While there are numerous genetic and toxin models of Parkinson’s disease, there is a relative paucity of models specifically for PSP,” says Fleming, who holds appointments in UC’s departments of psychology and neurology and rehabilitation medicine.  "This is a major impediment to the development of both symptomatic and disease-modifying therapies for PSP.

"The information gained from these studies will provide a better understanding of the relationship between environmental and genetic factors as they relate to PSP and importantly will generate a novel model of PSP,” says Fleming, adding that the development of such a model is an essential step toward the goal of being able to test potential therapeutics for PSP.

"Models are critical for the identification of novel targets for treatment,” says Fleming. "We are grateful for this generous gift and excited to establish a new line of research devoted solely to PSP here at UC. As researchers we take this responsibility very seriously and hope to make a significant contribution to the development of therapeutics for PSP.”