As a person ages, bone grafts start to fail. And while bone morphogenetic proteins have been shown to amplify bone growth, side effects, such as swelling, abnormal bone formation, and cancer, are a growing concern.
Philipp Leucht, MD, a
2010 OREF grant recipient, investigated how an alternative bone-promoting substance, Wnt3a, could be used to re-establish osteogenic capacity to bone grafts from the elderly. His research, which was funded in part by an OREF Career Development Grant in Total Joint and Trauma Surgery made possible by
Zimmer, was the subject of
a news report. The study was also published in the
July 2013 issue of The Journal of Bone and Joint Surgery.
A possible alternative to BMP?
A background in orthopaedic trauma inspired Dr. Leucht to learn more about the complex process of fracture healing. This led him to the laboratory of
Jill Helms, PhD, DDS, at Stanford School of Medicine. Dr. Leucht and Dr. Helms, who is also an OREF grant recipient, researched both the BMP and the Wnt pathways to understand more about the side effects of the former, and to test the ability of the latter to more safely accelerate bone healing. The Wnt pathway is important for both bone development and homeostasis and over the years Drs. Helms and Leucht used gain- and loss-of-function animal models, as well as agonists and antagonists to the pathway, to investigate the importance of Wnt signaling during fracture repair.
Roel Nusse, PhD, also at Stanford, first identified Wnt proteins and found a way to purify the Wnt3a protein, giving Drs. Leucht and Helms the opportunity to use it in their study. The doctors were not surprised to find that adding Wnt protein to a variety of bone injuries and implants resulted in exuberant bone formation and osseointegration.
Fountain of youth
Encouraged by these data, Dr. Leucht and his research team established multiple animal models in which they tested the safety and efficacy of the protein. Dr. Leucht believes that Wnt3a protein might be an alternative to BMP with fewer side effects, and have the ability to “rejuvenate” bone graft to osteogenic levels similar to those of young patients.
“Another advantage of this approach is that the incubation in the ex vivo environment results in no measurable carryover of Wnt protein into the host. Therefore, side effects are less likely to happen.”
The OREF grant, coupled with a grant awarded to Dr. Helms by the California Institute of Regenerative Medicine, has enabled Dr. Leucht to design preclinical trials for applying Wnt3a protein in spinal fusion and avascular necrosis of the femoral head.
“Extramural funding is limited, so it’s opportunities like those offered by OREF that allow new clinician scientists like me to explore research ideas and obtain preliminary data, which will help in obtaining future NIH funding. I cannot express how thankful I am to OREF and its donors for the opportunities they have provided me the last few years.”
About Dr. Leucht
Born in Germany, where he completed medical school at Ruhr University in Bochum and an orthopaedic trauma residency at the Johann Wolfgang Goethe University in Frankfurt, Dr. Leucht came to the United States in 2004 when he was offered a postdoctoral fellowship with Dr. Helms at Stanford School of Medicine. He completed a clinical fellowship in orthopaedic traumatology at Stanford and decided to continue his career as a clinician scientist in the United States. He was chief resident at Stanford before graduating in 2014. Dr. Leucht is currently a clinician scientist at New York University Hospital for Joint Diseases. He has an orthopaedic trauma practice and runs his own laboratory with a research focus on bone regeneration.