New Genetic Clues About Rare Brain Disorder

Progressive supranuclear palsy is a rare and devastating disease with no known treatments. New genetic clues could provide new insights into neurodegenerative therapies.

Three new genes linked to risk of PSP were identified and two additional genetic variants affecting risk were confirmed. The research, led by a team at Perelman School of Medicine at the University of Pennsylvania, marks the largest genetics study of the disease.

The discovery could aid in the discovery of treatments for Parkinson's and Alzheimer's disease.

The findings show that the disease has contrasts and similarities to other neurodegenerative diseases, including Parkinson's disease, frontotemporal dementia and Alzheimer's disease.

Dr. Gerard Schellenberg, PhD, professor of pathology and laboratory medicine in the Perelman School of Medicine at the University of Pennsylvania and the study's senior author said there is hope that the work this work will increase understanding of related more common diseases, such as Alzheimer's disease in addition to benefiting PSP patients.

The newly identified genes leading to added PSP risk include EIF2AK3, which clears potentially toxic misfolded proteins, STX6, that typically shuttles vesicles within the cell, and the third is MOBP, whose link is still unclear.

PSP is a form of frontotemporal dementia and only affects between three and six people per 100,000. After Parkinson's disease, it is the second most common cause of degenerative parkinsonism. Characteristics of the disease include difficulty coordinating eye movement, imbalance and gait instability, stiff movements, mood and emotional changes.

The study was based on genome wide association. It included studying 1,114 autopsy-confirmed cases of PSP and 3,287 control subjects. It also was repeated a second time.

There is currently no genetic test to measure PSP risk, but the findings could be a first step in understanding the genes associated with risk for PSP, which could someday lead to the ability to predict who is at risk of the disease. Researchers also can use the information gathered in the study to investigate a drug discovery target.

The work was funded by grants from organizations including CurePSP – Foundation for PSP |CBD and Related Brain Diseases, the Peebler PSP Research Foundation and the National Institutes of Health National Institute on Aging, National Institute on Neurological Disorders and Stroke and National Institute of Mental Health.