City of Hope awarded $4.5 million grant to investigate gene therapy treatment for AIDS.

National Medical Center and Beckman Research Institute has received a four-year, $4.5 million grant from the National Institute for Allergy and Infectious Diseases (NIAID) to investigate a gene therapy treatment for the human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS).

The study is designed to create a treatment that will prevent or delay the onset of AIDS by making the immune cells of HIV-infected patients resistant to HIV. To accomplish this, researchers are using ribozymes, or laboratory-modified "molecular scissors," engineered to recognize and sever the molecular materials necessary for the virus to replicate.

City of Hope is working in close collaboration with two other world-renowned medical centers, Children's Hospital Los Angeles and Loma Linda University, on this study. The study is part of the National Institutes of Health-sponsored Strategic Program for Innovative Research on AIDS Treatment, also known as SPIRAT.

"We have been committed since the 1980s to ongoing research investigating the use of gene therapy to treat a variety of diseases," said John Zaia, M.D., principal investigator of the study and director of Virology and Infectious Diseases, Division of Pediatrics, at City of Hope. "In 1991, we established the Gene Therapy Program to oversee and develop this research."

Stephen J. Forman, M.D., director of Hematology/Bone Marrow Transplantation at City of Hope, is co-principal investigator.

The idea of treating and curing diseases with gene therapy is nothing less than revolutionary. Within the human body, missing or mutated genes cause normal cell function to become distorted, which often leads to disease.

Rather than treating these genetic disorders with drugs designed to treat symptoms that may recur, gene therapists aim to develop the capability to provide permanent cures by altering the genetic makeup of cells.

Since the AIDS epidemic began in the early 1980s, nearly 1 million Americans have been infected by HIV. To date, nearly 400,000 of these individuals have developed AIDS, and more than 250,000 have died.

"The AIDS epidemic is taking place at the same time in medical history that the potential of gene therapy, one of medicine's most promising fields, is beginning to unfold," said Zaia. "We are applying the most recent findings in gene therapy to our search for a more effective treatment for HIV-positive individuals."

However, physicians and scientists agree that far more research must be conducted before the curative potential of gene therapy is realized and before it becomes accepted as standard treatment. The process of developing and perfecting gene therapy techniques will at least take years.

Founded in 1913, City of Hope is one of the world's leading research and treatment centers providing care for patients with serious ailments, including cancer, diabetes and infectious diseases. City of Hope, the largest provider of bone marrow transplantation services in California, is a National Cancer Institute-designated Clinical Cancer Research Center. -0-

                            FACT SHEET
                  CITY OF HOPE GENE THERAPY STUDY

-- Scientists suspect that gene therapy will eventually be used to
   treat or cure many of the 4,000-or-so known inherited diseases,
   as well as many other ailments, such as cancer, heart disease and
   AIDS, which result to an extent from impairment of one or more
   genes involved in the body's defenses.

-- HIV damages the human body by entering immune cells and
   replicating, thereby killing the host immune cells and creating
   new viral particles that attack other immune cells.

-- AIDS develops when the immune cells of HIV-infected patients are
   depleted to dangerously low levels.

-- A primary goal of the City of Hope study is to create biological
   vehicles, or "vectors," that will ensure the delivery of
   ribozymes to "target" stem cells.

-- In the first, or laboratory, phase of the City of Hope study,
   investigators are delivering ribozymes to target pluripotent, or
   blood-forming, stem cells collected from HIV-infected patients.
   Pluripotent stem cells produce T-cells and monocytes, which are
   key immune cells that HIV destroys.

-- Investigators hope that pluripotent stem cells genetically
   modified to carry the anti-HIV ribozyme will continuously produce
   offspring cells that also contain the ribozyme and are therefore
   HIV-resistant.

-- The second phase of the study will involve clinical trials on a
   preselected and limited number of HIV-infected patients.
   Researchers will collect blood from these patients from which
   pluripotent stem cells will be extracted and treated with
   anti-HIV ribozymes in the laboratory.  These stem cells will
   then be reinfused into the patients.

-- Researchers believe that the onset of AIDS will be delayed, or
   perhaps even prevented, if these genetically modified pluripotent
   stem cells produce HIV-resistant T-cells and monocytes.

CONTACT: City of Hope National Medical Center, Duarte

Paul Knopick, 800/888-5323