Finding drugs that may help prevent the spread of the deadly AIDS virus is the focus of a biotechnology research program at Utah State University.
Dr. Robert W. Sidwell, who heads the research project, said the USU effort is the second step in a nationwide testing effort that researchers hope will lead to development of drugs that prevent the spread of AIDS.Over the next five years, the university hopes to generate $6.4 million through five contracts to finance the research. The biggest share, $3.26 million, will come through a U.S. Army Medical Research and Development Command contract.
Other money will come from contracts with the National Institutes of Health, the USU Experimental Station and Biotechnology Center, and various pharmaceutical companies. Although the Army contracts do not deal specifically with AIDS research, they do involve a viral disease - Punta Toro - that shares many characteristics with AIDS, including the fact that it is thought to have originated in Africa.
Sidwell said the similarities between Punta Toro and AIDS could lead to a treatment for both.
Like AIDS, the Punta Toro virus suppresses the activity of the body's immune system, making the body more susceptible to infections and other diseases. Sidwell said the disease heavily affected U.S. soldiers during the north Africa campaign of World War II.
The contracts with the National Institutes of Health directly involve AIDS research. One is intended to develop antiviral drugs for treating human cytomegalovirus infections, particularly in AIDS and other immuno-suppressed patients, and the other is
o evaluate biological response modifiers as therapies for AIDS using animal models.
The other contracts will be used for various anti-viral development programs, most with a veterinarian emphasis.
Sidwell said, the USU program is the second step in the testing process. Drugs sent to USU have gone through a screening process involving cell cultures with favorable results. At USU, mice are used to take the evaluation a step further and those that show potential are passed on to other institutions involved with more expensive animal models such as cats or monkeys.
Seven projects are scheduled. In the first program, a mouse is inoculated with a disease closely resembling the immuno-suppressive disease induced by the human immunodeficiency virus. A series of biological-response modifiers is then evaluated for inhibitory effects. Those showing significant effects will then be studied in combination with known AIDS-inhibitory drugs such as AZT.
The second project involves therapy of opportunistic infections of AIDS patients. In this program, viruses known to cause serious diseases in AIDS patients, such as cytomegalovirus, herpes virus, and varicella zoster virus, are established in test-tube situations where they are treated in cell cultures with various anti-viral drugs.
The third project studies the spectrum of biochemical experiments in the first two projects to more fully determine their potential cytotoxicity and the mechanisms by which they inhibit the viruses. The purpose of this research is to determine the degree of selectivity and, therefore, potential safety of the virus inhibitors.
The fourth project involves drug targeting, or how to deliver the drugs to the infected cells while avoiding the non-infected cells. The researchers will also study the immunology, toxicology and pharmacology of the treatments.
The seventh project, which is still in the approval stage, would focus on transgenic animals, those with gene mutations.
"There are a lot of new drugs being developed with good potential, but they need to be tested on animals," Sidwell said. "The animal model allows us to mirror the retro-virus that causes profound immuno-suppression. We've developed many antibodies but these drive viruses into hidden places."