PHILADELPHIA - The National Institute on Aging of the National Institutes of Health has awarded Virginia M.-Y. Lee, PhD, the John H. Ware 3rd Endowed Professor in Alzheimer's Research in the Perelman School of Medicine at the University of Pennsylvania, a $7.5 million, five-year renewal grant to continue pioneering research on a debilitating neurodegenerative disorder.

Virginia M.-Y. Lee, PhD

The major goal of the Lee-led grant, which comprises years 16 to 20 of an ongoing series of clinical investigations, is to expand a Penn-based comprehensive research program studying the origins and progression of frontotemporal dementia.

Frontotemporal dementia refers to a group of rare disorders in which abnormal forms and amounts of a nerve cell protein (tau) cause the frontal and temporal lobes of the brain to shrink. Symptoms include out-of-place behavior, sudden mood changes, and decline or loss of speaking, writing, and reading capabilities. Experts describe the syndrome as comprising three related conditions: Pick’s disease, primary progressive aphasia, and semantic dementia.

 “My colleagues and I are grateful for this new cycle of funding,” said Lee. “Frontotemporal dementia can rob people of their personalities and basic ability to communicate. It is an insidious cluster of related conditions. While we continue to make progress in tracking down its underlying sources and how it does its damage, significant gaps in our understanding remain. This grant will enable us to continue the important work that has been taking place at Penn over the past 15 years, with an overall aim of earlier diagnosis, possible prevention, and eventual treatment.” 

While sometimes mistaken for the more common Alzheimer’s disease, frontotemporal dementia starts earlier, with an average age at onset of 54. Memory loss is one of the primary symptoms of Alzheimer’s. But in its early stages, frontal lobe dementia is not typically associated with memory loss. While there is currently no cure, a number of abnormal genes have been linked to the disease. 

Goals of the Penn grant include: 1) indentifying new genetic mutations that may cause, contribute to, or possibly prevent the disease; 2) classifying and understanding symptoms better; and 3) understanding how tau proteins can clump together, a major component of the disease.  

The project has several parts. Lee will provide overall coordination and oversight, as well as study the mechanisms of progressive cell-to-cell spread of abnormal tau protein in cell culture model systems. Murray Grossman MD, director of the Penn Frontotemporal Dementia Center, will collect clinical, neuropsychological, neuroimaging, genetic marker, and cerebrospinal fluid data to be used in each part of the project. He will also evaluate tau, a protein involved in many important cellular processes but which can clump, potentially triggering or contributing to frontotemporal dementia. The genetics component, led by Vivianna Van Deerlin, MD, PhD, a professor of Pathology and Laboratory Medicine, will continue to build a compendium of DNA samples for use in research. The fourth part, neuropathology and biomarkers, led by John Trojanowski MD, PhD, director of the Penn Institute on Aging, will conduct postmortem neuropathology studies on patients and controls. He will also test the hypothesis that different strains of pathological tau account for the variety of symptoms in mouse models. Gerard Schellenberg, PhD, a professor of Pathology and Laboratory Medicine, will examine the genetic and genomic (the totality of an organism’s genes) architecture of abnormal tau. Sharon Xie, PhD, a professor of Biostatistics, will provide statistical and data management support.

“The outstanding caliber of my co-investigators represents a source of hope that we will eventually be able to truly understand this syndrome and prevent and treat it in the future,” said Lee. “The work is exceptionally complex, but we’ve created a solid foundation for future progress.”

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $9.9 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $546 million awarded in the 2021 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 47,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2021, Penn Medicine provided more than $619 million to benefit our community.

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