Toxic Dump: A Breakthrough in Combating the Ill Effects of Anti-Rejection Drugs
Researchers have figured out a way to predict a child’s negative reaction to a commonly used anti-rejection medication. The next step will be to use the information to prevent or minimize such reactions.
Mycophenolate mofetil (MMF), a commonly used anti-rejection medication, is associated with gastrointestinal and hematological toxicity. Reducing the dosage may minimize toxicity, but can also increase the risk of rejection.
To understand how to use MMF more effectively, Jens Goebel, MD, medical director of kidney transplantation, and David Hooper, MD, fellow in the Division of Nephrology and Hypertension at Cincinnati Children’s Hospital Medical Center, are leading a multi-center collaborative project through the Midwest Pediatric Nephrology Consortium.
The study builds on pilot work by researchers in the Division of Clinical Pharmacology under Alexander Vinks, PharmD, PhD. It demonstrates an association between genetic variants in the main MMF-metabolizing enzyme uridine glucuronyl transferase and the risk of MMF-associated leukopenia.
Their work, recently published online in Clinical Pharmacology and Therapeutics, and Hooper’s ongoing project, are cornerstones of efforts led by Vinks and Goebel to better understand the pharmacogenetics of MMF.
Ultimately, researchers expect these efforts will allow them to predict individual patients’ responses to MMF and to personalize the dosing to avoid toxicity. “One size, even when adjusted for body surface area, clearly doesn’t fit all when it comes to MMF dosing,” says Goebel.
“There are better ways than just giving standard doses of these drugs, and in due course these types of technologies will be available worldwide to help patients,” adds Vinks.
Support for the study comes from grants from the Kidney Foundation of Greater Cincinnati, the Center for Research and Education in Therapeutics at Cincinnati Children’s and the University of Cincinnati Center for Environmental Genetics.
