MEDTIPS, December 1998
Indiana University School of Medicine
The strong link between high levels of oxidative damage to cells or DNA
in cells and conditions such as Alzheimer's disease, Parkinson's disease
and ALS (Lou Gehrig's disease) motivates researchers to identify the body's
enzymes that repair the damaged DNA. Indiana University School of Medicine
researchers are getting closer to understanding the oxidative DNA damage
which occurs daily in all cells of the human body as they take in oxygen
and use it for a variety of purposes. During this process, hydroxyl free
radicals are produced which attack the DNA and damage it. Molecular biologist
Mark Kelley, Ph.D., investigator in the Wells Center for Pediatric Research
at IUSM, is studying which of the body's DNA repair enzymes recognizes
various types of oxidative DNA damage and under what conditions the repair
enzymes protect cells. "We look at the healthy DNA and the damaged DNA
and work outwards. We identify the damage in the DNA, ask what enzyme
recognizes it and then we attempt to find what regulates and controls
that enzyme." He and colleagues are blocking the functions of different
repair proteins to see the effect on the cells. They are also producing
excess amounts of specific DNA repair genes to see if an increase of repair
protein makes a cell healthy.
A potential new weapon against sickle cell anemia has been developed
by Indiana University School of Medicine microbiologist Arun Srivastava,
Ph.D. Dr. Srivastava and colleagues believe a hybrid gene delivery vehicle
(vector) may hold promise for the treatment of a disease that affects
more than 90,000 Americans. Researchers have combined a virus called adeno-associated
virus 2 (AAV), which does not cause disease in humans, with a close cousin,
human parovirus B19, to develop a hybrid vector. The human parovirus B19
grows only in human bone marrow cells where red blood cells are made.
The new vector targets these cells, and may be useful in targeting malformed
sickle cells and delivering healthy genes to prompt the growth of "normal"
red blood cells. According to Dr. Srivastava, the discovery also shows
promise for treatment of hypercholesterolemia (high levels of cholesterol
in the blood) and restenosis (arteries that close after balloon angioplasty).
This novel gene delivery vector has yet to be tested in human trials.
Can cord blood cells grown in the laboratory (ex vivo expansion) be safely
transplanted into children who are undergoing stem cell transplant procedures?
If so, this would make stem cell transplantation available to many patients
who do not have a suitable bone marrow donor. Frank Smith, M.D., and his
colleagues at the Indiana University School of Medicine conducting preliminary
studies in cord blood transplantation have found that while stem cells
grown from cord blood are capable of reconstituting bone marrow function
in most children and smaller adults, non-engraftment (the bone marrow
is not reconstituted) is problematic, particularly in large children and
adults. One solution is to expand the number of cord blood cells in the
laboratory before the transplant is done. Once the team at IUSM and other
medical centers proves that this is a safe approach, they will place a
genetic marker into the expanded cord blood cells to see if the cells
are contributing to the growth of their patients' new bone marrow and
blood.
Patients treated for germ cell cancers (such as testis and ovarian) may
have a new course of treatment following high-dose chemotherapy and stem
cell transplantation. Twelve patients enrolled in an Indiana University
School of Medicine Phase I trial received modified bone marrow cells containing
a drug-resistant gene that promises to protect the healthy cells. The
researchers used engineered fibronectin fragments to assist in the transportation
of a retrovirus containing the drug-resistant gene into the patient's
bone marrow. The drug-resistant gene is designed to help patients tolerate
higher levels of chemotherapy after stem cell transplantation. Rafat Abonour,
M.D., medical director of the IU Stem Cell Laboratory, said the trial
provides evidence that human stem cells can be modified to contain a desirable
gene and persist in these patients over a long period of time.
New research on the life cycle of human hematopoetic stem cells reported
in a recent issue of the journal Blood has taken us closer to identifying
essential properties required by these cells for successful engraftment
in bone marrow transplantation patients. Using immunodeficient mice, Indiana
University School of Medicine researcher Edward F. Srour, Ph.D., and colleagues
have identified the exact stage [G0] at which a cell looses its inborn
ability to engraft. "It has been known for almost three decades that the
position of these cells in the cell cycle is important for their function.
Now we have identified the precise stage when ability to engraft deteriorates.
We hope to determine whether a cell, which has been induced to divide
and into which we have inserted a new gene, can return to G0 and again
have the ability to engraft and thus produce new bone marrow cells. This
potentially will have enormous impact on bone marrow transplantation."
Mi3, a venture capital partnership, has been set up to support developing medical imaging companies. IURA, Inc., the clinical practice arm of the Indiana University School of Medicine Department of Radiology was the first group to commit financing to Mi3, providing $5 million. The formation of Mi3 was announced Nov. 30 at the annual meeting of the Radiological Society of North America. The partnership expects to raise $25 million for investment in promising, young medical imaging companies. The partnership is unique in that it focuses on the application of imaging technology throughout the health care industry and can provide both medical and business expertise in early-stage ventures. Medical imaging currently represents $75 billion of U.S. health care expenditures. For more information, see http://www.Mi3.com.
CONTACT: Mary Hardin
317-274-7722
mhardin@iupui.edu
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