Jefferson Researchers Halt Immunological Diseases Using Potential New Drug Designed by Computer

Medical researchers at Jefferson's Kimmel Cancer Center (KCC) have demonstrated that an inexpensive molecule, identified using powerful computer systems at the center, significantly lessens the incidence and severity of several types of immunological disease in mice. A paper about this work appeared in the January 7, 1997 issue of Proceedings of the National Academy of Science.

The Jefferson investigators were led by Ziwei Huang, PhD, Assistant Professor and head of Rational Drug Design Research and Robert Korngold, PhD, Professor of Microbiology and Immunology at the KCC. They used computers and mice models to study the chain of events in cells that is the basis
of autoimmune disorders in humans, such as multiple
sclerosis (MS) and transplantation reactions, such as graft rejection and graft-versus-host disease (GVHD), which often occurs after bone marrow transplantation.

These researchers found computer-designed peptides and organic molecules that significantly inhibited the specific immune response in mice that leads to MS-like disease and skin allograft rejection. In addition, the mice exhibited no toxic side effects from the treatment.

"These new organic inhibitors may have important implications for the development of a new generation of nontoxic and orally available immunosuppressants for the treatment of autoimmune diseases and transplantation reactions," said Dr. Huang, who is an expert in rational drug design.

Bringing research breakthrough to therapy

The next step for the research team is to find out if effective drugs can be developed from this initial compound and applied in humans. In earlier studies, they developed a peptide that is highly effective in animal models of GVHD. Dr. Huang and Dr. Korngold are working closely with specialists at Jefferson's Bone Marrow Transplant Program to begin a multicenter phase I clinical trial in 1997 of this peptide drug's efficacy against GVHD in bone marrow transplant patients. In addition, the scientists will be undertaking studies of MS in humans in the near future. They hope that the initial trial of the peptide will lay the groundwork for future trials of one of the organic inhibitors developed in the current study.

"This is truly groundbreaking work," says Carlo Croce, MD, Director of the Kimmel Cancer Center. "Many other proteins discovered here at the center can be looked at in this way to design new drugs for other human diseases.

"The University has made a huge investment in translational research of which this effort is a major part. And it is paying off, " said Joseph S. Gonnella, MD, Dean of Jefferson Medical College and Senior Vice President for Academic Affairs.

Rational drug design will play a prominent role in Jefferson's mission to link basic research and patient care.

"Jefferson is fortunate to have such a dedicated and talented drug design team. I look forward to the future development of these translational research efforts," said Paul C. Brucker, MD, University President.