Penn has made a significant commitment to address public health issues related to an aging population through research programs that focus on aging and aging-related diseases - particularly brain diseases - and by establishing a network of partners to carry out this research and translate research findings to the clinic and the public-at-large.
At CNDR, the hypothesis that diverse neurodegenerative diseases arise from spreading and aggregation of toxic brain proteins links CNDR research programs. Clarification in any one disorder has a profound impact on understanding the mechanisms that underlie all of these disorders as well as on efforts to develop novel therapies to treat them.
In order to solve the intricate puzzle of neurodegenerative disease, scientists at CNDR are taking a variety of approaches:
Scientists use a basic science approach try to understand what goes wrong at the most basic, molecular and cellular level. At CNDR, the basic science program is led by Dr. Virginia M.-Y. Lee.
Some of the neurodegenerative diseases originate from mutations in genes. Even those diseases that are not strictly 'genetic' have some genetic component. At CNDR, the neurogenetics program is led by Dr. Jerry Schellenberg and Dr. Vivianna Van Deerlin.
Much of what is known about neurodegenerative disease comes from studies of brain tissue from both affected people and animal models of the disease. At CNDR, the neuropathology program is led by Dr. John Trojanowski. Researchers can request to obtain samples from the Tissue Research Bank for study.
Biomarkers are characteristics that can be objectively measured and that indicate the presence or state of a disease. They are extremely important for diagnosing disease and monitoring response to treatment. The search for biomarkers of neurodegenerative diseases at CNDR is led by Dr. Leslie Shaw, who is also the Biomarker Core Co-Director of the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Penn's Biomarker Core center for the Michael J. Fox Foundation's Parkinson's Progression Markers Initiative.
The focus of the Translational Medicine Program is on translating basic research discoveries into treatment approaches that will be useful in the clinical setting. At CNDR, this effort is led by Dr. Virginia M.-Y. Lee and Dr. John Trojanowski.
The long process of developing new drugs that will be useful in treating neurodegenerative diseases begins with the discovery of targets that, if modified, might affect the course of the disease. It includes the development of assays for evaluating the effect of different substances on those targets, the screening of hundreds of thousands of compounds to identify one or a few possible drug candidates, the optimization of these candidate drugs, and the testing of potential drugs in animal models of the disease and then in humans. The drug discovery effort at CNDR, which includes the Marian S. Ware Alzheimer Program, is led by Dr. Kurt Brunden, Dr. Virginia Lee, and Dr. John Trojanowski.
Research discoveries made in the laboratory must be tested in clinical settings in order to determine their effectiveness.
- Clinical research in Alzheimer's disease at CNDR is led by Dr. Jason Karlawish and Dr. David Wolk.
- Clinical research in frontotemporal degeneration and related conditions is led by Dr. Murray Grossman.
- Clinical research in Parkinson's disease is led by Dr. Howard Hurtig and Dr. Daniel Weintraub.
Biostatistics and Bioinformatics
Biomedical research in the 21st century results in the acquisition of enormous amounts of data. At CNDR, the management and analysis of data collected is led by Dr. Sharon Xie and Dr. Li-San Wang. The team is working on disease-related bioinformatics (aging, neurodegenerative diseases, and cancer), human genetics (including genome-wide association studies and whole-genome/whole exome resequencing studies), and computational methods for next-generation sequencing technology. They work collaboratively to analyze the Integrative Neurodegenerative Disease Database (INDD) from the Center for Neurodegenerative Disease Research (CNDR) that tracks ~11,000 patients who attended one of four neurodegenerative disease centers at Penn. This project hopes to lead to better characterization of disease progression, robust identification of controls and AD patients for clinical studies, and more sensitive early diagnosis of conditions such as Alzheimer's disease.
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