WASHINGTON _ A novel form of gene therapy can prolong with no apparent side effects the survival of T cells that are typically depleted during the course of HIV disease, a federally funded study has found.
The findings were reported in today's Proceedings of the National Academy of Sciences.
Study investigator Gary Nabel, of the University of Michigan, in Ann Arbor, called the results of the clinical trial "good news" for the biotech drug sector. "This was the type of clinical trial that showed you can get information without involving a large number of patients. The trial design facilitated discovery," he told BioWorld Today.
The study, which involved three patients at the University of Michigan Medical Center, was funded in part by the National Institutes of Health and the Howard Hughes Medical Institute.
SyStemix Inc., of Palo Alto, Calif., is conducting animal tests of a comparable autologous T cell gene therapy, said SyStemix patent attorney Meg Snowden. SyStemix is evaluating inserting stem cells with the rev M10 gene, the same gene used by the University of Michigan researchers. The goal is to equip a broader range of cells, such as T cells and macrophages, to resist HIV. (See BioWorld Today, Nov. 27, 1995, p. 1.)
The findings are the first report that gene therapy may be effective in boosting the immune systems of HIV patients. "The pilot study suggests that gene transfer can be used to prolong the survival of CD4+ T cells and may ultimately help to sustain the immune systems of HIV infected persons," said Nabel. Additional studies now under way would define the optimal approaches of CD4+ T cell gene transfer and determine the clinical efficacy of this approach, he said.
The study involved treating HIV-infected patients with their own CD4+ T cells that had been modified with an antiviral gene, thereby not requiring a donor who would need to be immunologically matched. Into these cells were inserted one of two altered HIV rev genes. Rev normally produces a protein that allows transport of certain HIV genetic materials within the infected cells from the nucleus to the cytoplasm, a critical step in viral replication.
Into half the cells harvested from each patient, the investigators inserted an altered rev gene that produces a defective protein, rev M10, which suppresses HIV replication by competing with the function of the normal rev. The altered rev gene was developed in the late 1980s by Bryan Cullen, of Duke University.
Into the other patients' cells, a dummy gene was inserted that produces a protein that does not compete with normal rev and consequently has no anti-HIV activity.
Both sets of cells were treated with interleukin-2 and then re-infused into the patients. The investigators found that the CD4+ T cells persisted longer than the cells with the dummy gene. None of the subjects developed any adverse effects from the therapy. n
-- Michele L. Robinson Washington Editor
(c) 1997 American Health Consultants. All rights reserved.