The Mayo Orthopaedic Genetic Host Variation Lab: Personalized Medicine of the Future?

by Elizabeth Hofheinz, M.P.H., M.Ed., February 4, 2020 Who, by their very genetic makeup, is predisposed to certain orthopedic conditions? This is what Matthew P. Abdel, M.D., Director of the Orthopedic Genetic Host Variation Laboratory at Mayo Clinic in Rochester, Minnesota, is aiming to find out. Dr. Abdel, a Professor of Orthopedic Surgery at Mayo, has been awarded an NIH R01 grant to study arthrofibrosis after total knee arthroplasty. Dr. Abdel, who began this lab while still a resident over a decade ago, told OSN, “While in the oncology field, for example, no two breast cancer patients are treated the same based on their individual genetic makeup, in orthopedic surgery we have traditionally lacked such ability. We have patients who have the same surgeon and the same implant and react differently. But the fact is that different patients will respond differently based on their genetic makeup.” Dr. Abdel, who has a background in biochemistry, notes, “There are seemingly countless things that can put the success of a surgery at risk. One of them is arthrofibrosis. Stiffness after knee surgery is a common complaint and one for which we have few solutions. Indeed, for a subset of patients, there are no prosthetic, anesthetic, or surgical solutions.” Dr. Abdel’s work, which even garnered attention from the Wall Street Journal, has also involved a Knee Society grant. “There is robust scar tissue formation that occurs in a subset of patients. We have come to believe that these individuals have an underlying pathologic phenotypic response. At present, we have a large multicenter study with 130 patients where the treatment arm involves MUA at six weeks, while a second arm includes MUA plus two medications.” And the big response that is kicked off by scar tissue formation? Inflammation. “We use anti-inflammatory medications such as celecoxib, aspirin, IV dexamethasone, and IV ketorolac to regulate the inflammatory cascade. But those are only temporary solutions, of course.” Dr. Abdel, who conducts dozens of studies annually on this topic, notes, “If we cannot identify at-risk patients up front, then we cannot adjust surgical techniques, pharmacotherapies and follow-up treatment.” “Our ultimate goal is to have preoperative blood tests with routine labs indicating if someone is high, medium, or low risk. Then, if someone is high risk we can intervene appropriately. If someone appears to be low risk but is having problems at a later date, then we can add pharmacotherapies.” Another area that Dr. Abdel’s lab is tackling is the metal on metal issue. “We have identified genes that we think might make someone more predisposed to metal debris than other individuals. We had never suspected that individuals with adverse local tissue responses might have an underlying genetic issue.” “Our team is studying the impact of metal ions on cells. We suspect that cells from certain patients will react poorly to these metal ions.”

The Mayo Orthopaedic Genetic Host Variation Lab: Personalized Medicine of the Future?

Elizabeth Hofheinz

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