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Contacts: Karen Young Kreeger or Franklin Hoke: (215) 662-2560 |
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March, 1998 Science Tip Sheet Below are three story ideas based on ongoing research at the University of Pennsylvania Medical Center. Smell Loss: an Early Indicator of Alzheimer's and Parkinson's Diseases Changes in a person's ability to detect and identify smells can be one of the earliest signs of several neurodegenerative diseases, according to a number of recent studies at Penn's Smell and Taste Center. Long before clinical signs of mental or motor impairment become pronounced in these diseases, the ability to ascertain and interpret odors shows dysfunction, notes center director Richard L. Doty, Ph.D. "Our research indicates that smell loss is among the first signs of Alzheimer's disease, Parkinson's disease, and several other neurodegenerative disorders," Doty says. "Furthermore, tests of smell can allow us to differentiate between closely related and often confused disorders, such as Parkinson's disease and progressive supranuclear palsy." The center was founded in 1980 as the first of five such centers funded by the National Institutes of Health, and researchers at the center, as one of their first tasks, sought to develop reliable quantitative assessment techniques for the sense of smell. The result was the most widely used clinical olfactory test in the world, the University of Pennsylvania Smell Identification Test (UPSIT), which has served as the basis for many subsequent studies of smell in health and disease at Penn and elsewhere. Other recent investigations at the center have shown that blindness, per se, does not enhance the sense of smell, despite anecdotal evidence to the contrary, and that head trauma is one of the most common causes of smell dysfunction after upper respiratory, nasal, and sinus infections. Newly Found Endothelial Receptor Implicated in Both Heart Disease and AIDS While looking for cell-surface receptors important to the biology of blood vessels, researchers in Penn's Institute for Medicine and Engineering serendipitously discovered that some of the vessel-lining cells (endothelium) they were studying contained a chemokine receptor called CXCR4. This molecule was recently found to be an important cofactor in HIV-1 infection by Penn researchers and others. "This was unexpected," says institute director Peter F. Davies, Ph.D. "We weren't looking for these receptors with HIV in mind. The focus of our study was to find chemokine receptors involved in signal-transduction pathways important in such cardiovascular diseases as atherosclerosis." Evidence that HIV infects endothelium is limited, but in some studies, HIV has been found in the vessel linings in a few special cases, for example brain capillaries in AIDS patients with dementia and the placental tissue from HIV-positive mothers. "The endothelium is the first tissue with which blood-borne virus will come into contact," notes Davies, who is a professor of pathology and laboratory medicine and of bioengineering. "Therefore, there might be a case for CXCR4 or other chemokine receptors facilitating HIV entering some types of endothelial cells." Because the endothelial cells are the gatekeeper cells at the blood-tissue interface, it might become a useful target -- in some cases -- for chemokine-related intervention. In atherosclerosis, the scientists speculate that CXCR4 may play a role in the accumulation of cholesterol-laden leukocytes in artery-clogging plaques, and so be important to understanding the pathology of heart disease. "It is unclear whether these findings are related to any association between HIV infection and clinical heart disease," remarks Davies. This study was reported in the January issue of Biochemical and Biophysical Research Communications. DNA Vaccination Lowers HIV-1 Viral Load in Infected Chimpanzees An experimental vaccine incorporating DNA derived from two of the nine genes of HIV-1 is capable of stimulating an enhanced immune response in infected chimpanzees, recent investigations show. Chimpanzees injected with the new vaccine demonstrated higher levels of antibodies against the virus and, more importantly, their viral loads subsequently dropped. The results, published in the December issue of The Journal of Infectious Diseases, suggest that humans infected with the AIDS virus may benefit from similar immunizations. "The implication of this study is that, by stimulating the immune system, we can lower virus replication in infected individuals," says David B. Weiner, Ph.D., developer of the vaccine technology and an associate professor of pathology and laboratory medicine. "It gives hope that immune therapy involving a DNA vaccine, in the context of other therapies, may be useful in the treatment of AIDS." The findings mark the first time any therapy involving a form of immunization has been shown to lower HIV-1 viral load in chimpanzees, according to Weiner. Chimpanzees, like humans, are susceptible to HIV-1 infection, although they generally do not progress to overt disease. Based partly on the strength of this new data, a 21-patient phase-I clinical trial was launched in late January that combines proven antiretroviral drug therapy with DNA vaccination in an attempt to eradicate HIV-1 in humans infected with the virus. The trial is being conducted under the supervision of Rob Roy MacGregor III, M.D., a professor of medicine and director of AIDS clinical trials at Penn. The University of Pennsylvania Medical Center's sponsored research and training ranks third in the United States based on grant support from the National Institutes of Health, the primary funder of biomedical research and training in the nation -- $175 million in federal fiscal year 1997. In addition, for the third consecutive year, the institution posted the highest annual growth in these areas -- 17.6 percent--of the top ten U.S. academic medical centers. News releases from the University of Pennsylvania Medical Center are available to reporters by direct e-mail, fax, or U.S. mail, upon request. They are also posted electronically to the medical center website (http://www.uphs.upenn.edu), to EurekAlert! (http://www.eurekalert.org), sponsored by the American Association for the Advancement of Science. |
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