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September 2000 News
Five Alternatives Researchers Receive Grants
September 12, 2000
The Alternatives Research & Development Foundation (ARDF) recently announced five grant recipients for 2000. As part of its continuing effort to encourage the use of alternatives to animals in basic research, product testing, and education, ARDF offers annual awards of up to $40,000 to research aimed at developing alternative methods. This year's recipients are working to replace the use of animals in such diverse areas of research as burn injury, HIV vaccination and infection, and the mechanisms of drug penetration in the central nervous system.
Dr. Charles W. Hewitt, University of Medicine and Dentistry of New Jersey, received a continuation grant for his project designed to develop an "In Vitro Burn Injury Model Using Bioengineered Human Living Skin Equivalents." In response to concerns regarding the pain and distress associated with using animals in burn research, Dr. Hewitt developed a series of experiments using a three-dimensional human tissue culture model, without the use of animals, to further his studies on complete surgical reconstruction and cosmetic restoration of burn patients. This "humanized" bioartificial skin construct (BSC) which, unlike other models, includes a dermis component, demonstrates the morphological and histopathological changes and cellular mechanisms of injury similar to those seen in thermally injured human skin.
Dr. Damir Janigro, Cleveland Clinic Foundation, will continue his project on the "Validation of an In Vitro Model for the Blood-Brain Barrier." The purpose of this project is to establish an in vitro model of the human blood-brain barrier (BBB) for testing central nervous system (CNS) drug permeation. Dr. Janigro has developed a novel tridimensional and dynamic model of the BBB that faithfully reproduces mechanisms of drug exclusion and transport at the BBB. The long-term goal of this proposal is to determine the prediction value and thus the usefulness of this model system for evaluating the CNS potential for pre-clinical pharmacological studies. To date, owing to the pitfalls of the currently available in vitro models, studies are performed in vivo on rodents or other small animals. The results of these animal studies cannot be directly extrapolated to human tissue.
Dr. Phillipe Arnaud, Medical University of South Carolina, received a grant for his project on "Recombinant Fetuin as a Replacement for Fetal Bovine Serum." Fetal bovine serum (FBS), derived from the fetuses of pregnant cows killed in slaughterhouses, is sold to research laboratories as an essential nutrient to support cell cultures. The effects of FBS on cell maintenance and growth recently has been attributed to fetuin, the major protein in FBS. The ultimate goal of Dr. Arnaud's work is to provide scientists with recombinant native fetuin to replace the use of FBS. In addition to preventing the unnecessary slaughter, pain and distress of animal fetuses, this effort will provide the scientific community with a well-defined supplement devoid of microbial, viral and fungal contaminants, which will render cell culture results more reproducible within and between laboratories.
Dr. David Schwartz, Johns Hopkins University, received support for his work on "Human In Vitro and In Vivo Alternatives to Animal Studies on HIV Vaccination and Infection." Thousands of primates and millions of mice will be used over the next decade in the development of vaccines and drugs, in part because investigators kill the animals to retrieve organs and lymph nodes. Dr. Schwartz developed positron emission tomography (PET) scanning as a safe, noninvasive technique to examine activated lymph nodes and spleens of humans responding to vaccines or viral infections. The long-term objectives are to diminish the use of animal models of human immunity by offering a real-time, noninvasive, safe and reproducible method of localizing, quantifying and imaging specifically activated lymphocytes in lymph nodes and organs of human subjects.
Dr. Bingfang Yan, University of Rhode Island, received support for his project on "Prediction of Human CYP3A Induction by a Receptor-Activator Based Method." Cytochrome P4503A (CYP3A) enzymes, the most abundant of the P450 enzymes, serve as the body's principal system for handling toxic substances or similar materials it wants to remove. They are involved in the metabolism of two-thirds of all drugs and other foreign chemicals. Substances that "induce" these enzymes -- i.e., accelerate their synthesis -- profoundly affect how a drug will act upon the body and how it may interact with other drugs. They also relate to the efficacy of a drug -- for example, a drug that causes a major activation of these enzymes may be eliminated from the body too quickly. The Food and Drug Administration, therefore, asks pharmaceutical companies to test new drugs for CYP enzyme induction. Currently, this testing depends upon the use of human liver cells and large numbers of laboratory animals. The long-term goal of Dr. Yan's project is to develop an in vitro method to screen for CYP inducers, eliminating the use of animals.
For more information about the Alternatives Research and Development Foundation or their grants program write to ARDF, 14280 Golf View Drive, Eden Prairie, MN 55346-3000, or e-mail: ardfjmc@aol.com.