Toronto Researchers Use Gene Therapy to Show Genetic Material Promotes
Blood Production and Preserves Bone Marrow Cells
(Toronto, November 6, 1996) ... Researchers at The Toronto Hospital
in collaboration with scientists at Genetics Institute, a Boston biotechnology
company, have discovered that a gene which promotes blood development also
protects the cells responsible for the life-sparing effects of bone marrow
transplantation. The finding was made possible by the use of a gene therapy
technique developed by the Hospital team.
Interleukin 11 is a hormone-like factor which stimulates the production
of blood cells responsible for clotting (platelets) and those responsible
for fighting bacterial infection (granulocytes). The study showed that interleukin
11 also protects stem cells found in bone marrow. Stem cells produce all
the different components of blood and are used to perform bone marrow transplants.
"This study demonstrates the new gene continues to be expressed in
serial bone marrow transplantation and continues to promote blood development,"
says Dr. Robert Hawley, principle investigator and Scientific Director,
Oncology Gene Therapy Program, The Toronto Hospital, and Associate Professor
of Medical Biophysics and Medicine, University of Toronto.
The interleukin 11 gene was first inserted into bone marrow cells from donor
mice using a retroviral vector known as the murine stem cell virus vector,
a genetically-engineered defective version of a naturally occurring mouse
virus. The modified bone marrow was then transplanted into a group of recipient
mice. The transplanted bone marrow with the new genetic material was then
retransplanted into a second group of mice. Tests showed that platelet and
granulocyte counts stabilized faster in the experimental groups compared
to control groups which received bone marrow containing the empty retroviral
vector. In addition, the group with the interleukin 11 gene continued to
have higher levels of platelets once the blood forming system returned to
its steady state.
Most importantly, however, only the bone marrow which expressed the interleukin
11 gene had enough reserve capacity remaining after two transplants to be
able to reconstitute the blood forming system in a third group of mice.
"This shows that interleukin 11 is a pharmacologic regulator of platelet
production," says Dr. Hawley, "but it must also function as a
maintenance factor for bone marrow stem cells. If the interleukin 11 gene
was shut off, as is frequently observed with genes inserted by other retroviral
vectors, we would not have made this discovery."
Recombinant interleukin 11 is currently undergoing clinical testing to improve
platelet and granulocyte counts in cancer patients after therapy. The new
results suggest that another application for recombinant interleukin 11
might be to maintain stem cells in culture during the period required to
introduce the therapeutic gene in any gene therapy procedure.
New "Gene Therapy" Technique
The goal of current gene therapy research is to devise an efficient method
to introduce the therapeutic gene into all of the stem cells so that when
they are returned to the patient they will continue to produce blood cells
expressing the therapeutic gene for the lifetime of the patient. "This
study shows that the retroviral vector (the gene carrier) which we have
developed has the potential to achieve this goal," says Dr. Hawley.
New Grant
The findings, published in the September issue of the Proceedings of the
National Academy of Sciences, will be further investigated in a study focusing
on human stem cells. Dr. Hawley's team has just received a grant from the
Red Cross/Bayer Research and Development Fund to optimize the retroviral
vector technology for ultimate use in patients.
Bone Marrow Transplantations
Bone marrow transplants are currently used to treat a number of cancers
of the blood including leukemia and lymphoma, as well as other types of
cancer such as breast cancer. Recipients receive either their own bone marrow
or bone marrow from a matched donor. In the future, gene therapy may allow
bone marrow transplants to be used for the treatment of other diseases involving
blood cells. Prime candidates for this form of treatment are thalassemia
and sickle cell anemia and severe combined immune deficiency.
For further information, contact Josey Panetta, Senior Media Relations
Officer, The Toronto Hospital, (416) 340-3303.