For more than 50 years, the Pharmacology and Toxicology Department at the University of Utah has been recognized internationally as a center of excellence in anticonvulsant research and development. Over this period, departmental faculty have authored more than 600 epilepsy-related works and many of today's standard laboratory tests for the evaluation of potential antiepileptics have evolved from these research studies. Such faculty efforts have also resulted in numerous national and international awards. Particularly significant examples include: the John J. Abel Award in Pharmacology (American Society for Pharmacology and Experimental Therapeutics; Dixon Woodbury) and the Epilepsy Research Award (American Epilepsy Society; Ewart Swinyard). Moreover, many of the department's Ph.D. graduates have gone on to earn recognition in epilepsy-related research. A recent example is the award to Dr. Nanda Singh of the 1998 Eric Lothman Research Training Fellowship (American Epilepsy Foundation).
Departmental faculty share their epilepsy-related expertise in collaborative research projects with colleagues within and without the Health Sciences and enjoy productive scientific relationships with local, national and international companies in the pharmaceutical and biotech industry. Current examples of such local relationships include collaborative efforts with NPS Pharmaceuticals and Cognetix.
The centerpiece for the department's epilepsy-related research is The Anticonvulsant Drug Development (ADD) program. The primary purpose of this program is to identify potential new antiepileptic agents and the work is funded by a long-term NIH research contract for The Early Evaluation of Anticonvulsant Drugs.
This project is a component of an extensive Epilepsy Therapeutics Research Program directed toward identifying potential new antiepileptic agents to be used in humans. The ADD program operates under the aegis of the Epilepsy Branch, Division of Convulsive, Developmental and Neuromuscular Disorders, NINDS/NIH and has received continuous support from this agency since 1975. To date, such support totals ~$27M. This represents some 25% of all the research funds provided to the University of Utah by NINDS (NIH) during this time frame. The program is directed by Dr. Harold H. Wolf and Dr. H. Steve White (Principal Investigator). Other Health Sciences faculty from within and without the Department of Pharmacology and Toxicology participate in this effort.
The program also provides a site for research training of undergraduate students, departmental and extra-departmental graduate students, postdoctoral fellows and visiting scientists. Over the years, more than 100 such individuals have received training in the ADD program. Additionally, faculty aligned with the program routinely provide instruction to professional students in the College of Pharmacy and the School of Medicine.
The research component of the program utilizes appropriate animal models in the preclinical assessment of some 1000 new compounds per year. Major considerations in characterizing a candidate compound's potential utility are: identification, quantification and evaluation of anticonvulsant activity; quantitative determinations of neurotoxicity; and evaluation of the compound's ability to induce tolerance or activate liver drug-metabolizing enzymes following subchronic administration. Effective compounds are subjected to additional investigation to delineate mechanism of action and to permit comparisons with standard, prototypical anticonvulsants. Promising compounds which exhibit a high level and/or unusual spectrum of anticonvulsant activity with superior therapeutic indices are selected for detailed toxicological evaluation (elsewhere) and are subsequently advanced to clinical trial in humans. An important component of the project involves the development and validation of new animal models for predicting the efficacy of novel antiepileptic agents.
This research project has been involved in the preclinical evaluation of every new anticonvulsant introduced to clinical use in the USA during the past 20 years.