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[IP] New study demonstrates bone protein can reverse kidney failure

New study demonstrates bone protein can reverse kidney failure

Public release date: 26-Jun-2003

Contact: Bonnie Prescott
email @ redacted
Beth Israel Deaconess Medical Center

New study demonstrates bone protein can reverse kidney failure
BOSTON - A new study led by investigators at Beth Israel Deaconess Medical
Center (BIDMC) has shown that a protein used to heal fractured bones is
effective in repairing and reversing chronic renal disease, a leading cause
of morbidity and mortality throughout the U.S.
These findings, which are reported in the July 2003 issue of Nature
Medicine, could help lead to the development of a therapeutic alternative
for the nearly 300,000 kidney disease patients who are currently undergoing

"Dialysis is not really a treatment, it's just a means of survival until an
opportunity for a transplant opens up," notes the study's senior author
Raghu Kalluri, Ph.D., director of the Center for Matrix Biology at BIDMC and
Associate Professor of Medicine at Harvard Medical School. "This is a very
tedious way of living life," he adds, explaining that the process of
mechanically filtering blood through a machine to remove waste products must
be performed several times a week for a period of three to four hours per
visit, posing risks of infection and other side effects. Furthermore, the
procedure is extremely costly.

The kidneys function as a filtration system, keeping the body's blood supply
healthy by removing excess fluids and wastes, as well as by producing
hormones. When kidneys "fail" - as can result from complications associated
with diabetes, lupus or several other diseases - harmful wastes accumulate
in the bloodstream, excess fluids build up in the body, and red blood cell
production is impeded. Once chronic kidney disease develops, it cannot be
reversed or repaired; when the organs cease to function, patients have no
alternative but to undergo dialysis while awaiting a kidney transplant.

This new study looked at the role of a molecule called bone morphogenic
protein (BMP)- 7 which, in its recombinant form, has been approved by the
U.S. Food and Drug Administration for the treatment of bone fractures.
Earlier studies had revealed that BMP-7 is highly expressed in the kidneys
of healthy individuals. "We wanted to learn if this protein was somehow
offering protection against kidney injury," explains Kalluri.

The investigators used mouse models of chronic renal injury, characterized
by the presence of scar tissue known as renal fibrosis; once kidney disease
was well-established in the animals, they administered human recombinant

"We found that in the kidneys, BMP-7 reverses a process known as
epithelial-to-mesenchymal transition, which generates scar-causing cells
known as fibroblasts," says Kalluri, explaining that BMP-7 first reduces the
number of the fibroblast cells, and then replaces the damaged areas of the
kidney tubules with healthy epithelial cells. "In effect," he adds, "BMP-7
is decreasing the bad cells [in this context, fibroblasts] and converting
them into good cells [in this context, epithelial cells]."

Although therapies exist to slow progression of kidney disease, once it has
developed it becomes intractable, eventually leaving patients no alternative
but to undergo dialysis. "The possibility of creating a cost-effective drug
that would actually reverse renal injury could significantly reduce the need
for dialysis and significantly improve the quality of life for these
patients," says Kalluri.

Study co-authors include BIDMC investigators Michael Zeisberg, M.D.,
Jun-ichi Hanai, M.D., Hikaru Sugimoto, M.D., Ph.D., Tadanori Mammoto, Ph.D.,
David Charytan, M.D., and Frank Strutz, M.D.

This study was funded by grants from the National Institutes of Health,
Deutsche Forschungsgemeinschaft, and support from the Center for Matrix
Biology, BIDMC. Ortho Biotech Products, L.P., is the exclusive licensee of

Beth Israel Deaconess Medical Center is a major patient care, teaching and
research affiliate of Harvard Medical School, and ranks third in National
Institutes of Health funding among independent hospitals nationwide. BIDMC
is clinically affiliated with the Joslin Diabetes Center and is a founding
member of the Dana-Farber/Harvard Cancer Center. BIDMC is the official
hospital of the Boston Red Sox.
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