Childrens Hospital Study Could Help Surgeons Predict
Which Transplant Recipients Would Experience
Rejection/Tailor Medication
Rakesh Sindhi, MD, has been awarded a $1.1
million grant from the National Institutes of Health.
PITTSBURGH Oct. 11, 2006 A Childrens Hospital of
Pittsburgh of UPMC transplant surgeon and researcher has
received a grant from the National Institutes of Health to
study genetic factors that could predispose transplant
recipients to rejection.
The goal of the four-year, $1.1 million grant is to study
these factors in order to predict before transplant which
patients are more likely to experience rejection. This
information may be used to tailor anti-rejection medications
accordingly, according to Rakesh Sindhi, MD, co-director of
Childrens Hillman Center for Pediatric Transplantation and
principal investigator of the study. He plans to enroll 80
children receiving liver transplants at Childrens.
Based on the results of this study, a patient more likely to
reject a transplanted organ may someday receive high doses
of anti-rejection medicine initially. Those who are less
likely to reject could have lower doses, or less potent
combinations, said Dr. Sindhi, an associate professor of
surgery at the University of Pittsburgh School of Medicine.
By applying individualized anti-rejection strategies before
the transplant even occurs, we hope to reduce rejection
rates and drug-induced side effects for pediatric liver
transplant from 50 percent to about 20 percent.
Surgical techniques have improved survival rates for
pediatric organ transplantation dramatically over the last
25 years. As a result, the challenge has shifted to
improving quality of life. Anti-rejection medications are
important because, while they make transplantation possible,
they also can have adverse side effects that can themselves
become life-threatening, such as infections and cancers.
Researchers will study the multiple processes that cause
rejection in blood cells. This information will be linked to
the unique genomic fingerprint of a liver transplant
candidate, based on the inheritance of more than 500,000
mutations from parent to child. These mutations, known as
nucleotide polymorphisms, represent misspellings in the
genetic code, are present in all people and form the basis
of inherited predisposition to a variety of diseases and
outcomes, according to Dr. Sindhi.
There is evidence from our earlier research that these
mutations can be transmitted from parent to child in certain
patterns that indicate if a transplant candidate is
predisposed to rejection, a rejection-free state or
tolerance, a rare occurrence whereby anti-rejection
medications no longer are required, he said. Any tool that
could help guide us in deciding when and by how much to
lower anti-rejection medications would be invaluable in
improving the quality of life for our patients.
Dr. Sindhis grant is from the National Institute of Allergy
and Infectious Diseases. Grant collaborators include: the
Genetics and Proteomics Laboratories at Pitt; the Department
of Human Genetics at Pitt; Duke University; and the EMMES
Corporation in Bethesda, MD.
For more information about Dr. Sindhis research or the
Hillman Center for Pediatric Transplantation at Childrens,
please visit www.chp.edu.