WASHINGTON _ A novel form of gene therapy can prolong withno apparent side effects the survival of T cells that are typicallydepleted during the course of HIV disease, a federally funded studyhas found.

The findings were reported in today's Proceedings of the NationalAcademy of Sciences.

Study investigator Gary Nabel, of the University of Michigan, in AnnArbor, called the results of the clinical trial "good news" for thebiotech drug sector. "This was the type of clinical trial that showedyou 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 ofMichigan Medical Center, was funded in part by the NationalInstitutes of Health and the Howard Hughes Medical Institute.

SyStemix Inc., of Palo Alto, Calif., is conducting animal tests of acomparable autologous T cell gene therapy, said SyStemix patentattorney Meg Snowden. SyStemix is evaluating inserting stem cellswith the rev M10 gene, the same gene used by the University ofMichigan researchers. The goal is to equip a broader range of cells,such as T cells and macrophages, to resist HIV. (See BioWorldToday, Nov. 27, 1995, p. 1.)

The findings are the first report that gene therapy may be effective inboosting the immune systems of HIV patients. "The pilot studysuggests that gene transfer can be used to prolong the survival ofCD4+ T cells and may ultimately help to sustain the immune systemsof HIV infected persons," said Nabel. Additional studies now underway would define the optimal approaches of CD4+ T cell genetransfer and determine the clinical efficacy of this approach, he said.

The study involved treating HIV-infected patients with their ownCD4+ T cells that had been modified with an antiviral gene, therebynot requiring a donor who would need to be immunologicallymatched. Into these cells were inserted one of two altered HIV revgenes. Rev normally produces a protein that allows transport ofcertain HIV genetic materials within the infected cells from thenucleus to the cytoplasm, a critical step in viral replication.

Into half the cells harvested from each patient, the investigatorsinserted an altered rev gene that produces a defective protein, revM10, which suppresses HIV replication by competing with thefunction of the normal rev. The altered rev gene was developed in thelate 1980s by Bryan Cullen, of Duke University.

Into the other patients' cells, a dummy gene was inserted thatproduces a protein that does not compete with normal rev andconsequently has no anti-HIV activity.

Both sets of cells were treated with interleukin-2 and then re-infusedinto the patients. The investigators found that the CD4+ T cellspersisted longer than the cells with the dummy gene. None of thesubjects developed any adverse effects from the therapy. n

-- Michele L. Robinson Washington Editor

(c) 1997 American Health Consultants. All rights reserved.