Jefferson Researchers Breaking New Ground to Attack AIDS With Pioneering
Jefferson researchers led by Roger J. Pomerantz, MD, chief,
medicine's infectious diseases, and director, Center for Human Retrovirology,
are breaking new ground in research efforts to fight AIDS by pioneering
gene therapy approaches.
By using gene therapy rather than traditional medication treatments, the
researchers' goal is to turn AIDS into a chronic disease that can be treated
and managed much the same as diabetes and heart disease.
The proposal to begin using gene therapy to treat HIV-1-infected patients
has been approved by the National Institutes of Health (NIH), and the Federal
Drug Administration (FDA) has given approval to move forward with the project.
The proposed treatment, called "intracellular immunization," builds
upon earlier Jefferson research. It would become part of clinical trials
to introduce to humans a genetically constructed antibody that laboratory
studies show can inhibit HIV-1 virus growth within their cells.
Jefferson's studies are among a very few in the world to take a gene therapy
approach to AIDS treatment, says Dr. Pomerantz.
"This will be only the second or third gene therapy for HIV worldwide.
We're especially proud of the undertaking because it was entirely developed
at Jefferson," he explains.
"This is all a homegrown technique, involving a number of Jefferson
departments, laboratories and staff. We are cautiously optimistic of its
Research Leads to Treatment
The decision to take a gene therapy approach to treating HIV disease or
AIDS resulted from encouraging basic research studies done at Jefferson
a few years ago.
What is called "intracellular immunization" would provide an alternative
to administering medication to patients. Instead, patients' cells would
be treated with a molecular construct making the cells resistant ­p;
in effect, "immune" ­p; to HIV replication.
Results of the previous laboratory studies were published in the Proceedings
of the National Academy of Sciences, Human Gene Therapy and the Journal
of Virology. The proposal to the FDA calls for clinical trials to begin
in human patients within the next year.
Patients would be reinfused with HIV-resistant cells at Jefferson's Clinical
Research Center. If production of gene therapy constructs goes smoothly,
Dr. Pomerantz hopes these treatments could begin this year.
New Treatment Takes Innovative Approach to HIV
The Jefferson researchers are among the few in the world to view HIV more
as a disease of DNA than as an infectious disease, Dr. Pomerantz explains.
"One way to approach diseases of DNA is through gene therapeutic means,"
Such an approach is "not easy," the infectious diseases chief
"It means you can't be good at just one thing. You have to be able
to do both the basic and translational research, and also have a clinical
center. Lots of places have a good clinical center, and lots do good basic
research, but Jefferson is one of the very few to try to put all the pieces
together in one location."
The interdepartmental approach draws on researchers and resources from the
department of medicine as well as the Kimmel Cancer Institute and the newly
established Center for Human Retrovirology.
While Not a Cure, Gene Therapy Could Extend Life Span
He emphasizes that gene therapy is not a "cure" for AIDS. Rather
it offers a chance to turn AIDS into a "chronic disease," one
that can be treated and managed much like other diseases such as diabetes
and heart disease.
"This is not to say gene therapy would not be analogous to a cure.
It would be great if we could keep viral replication to almost zero. That
would give people a normal life span while the disease is treated and better
managed. Wouldn't it be something to change a disease that now claims fatalities
within an average of 7 years to, say, 50 years? That's our long-range goal,"
Dr. Pomerantz concludes.