New Study Suggests Aurora Kinase A Signaling Pathway Involved in GVHD

There is some good news to report when it comes to graft-versus-host disease (GVHD). Researchers at Seattle Children’s Research Institute lab have discovered a genetic pathway that can be targeted with existing drugs to prevent GVHD.  In a study just published in the journal Science Translational Medicine, they write that a drug which inhibits the aurora kinase A signaling pathway may help patients who acquire GVHD.

The researchers examined the gene expression profile of nonhuman primate T cells during acute GVHD and demonstrated that pharmacologic inhibition of aurora kinase A could improve survival in a mouse model of GVHD.  Aurora kinase A proteins are important for cell division and proliferation in human cells. Defects in the aurora kinase A gene can cause cells to overproliferate and lead to cancers.

“This is a mysterious disease that has perplexed doctors who treat bone marrow transplant patients for decades,” said lead study author Leslie Kean, MD, who is a pediatric cancer specialist at Seattle Children’s Research Institute, Seattle, in a press release. “We can cure patients of leukemia and other diseases with bone marrow transplants, but many of those patients get GVHD. In extreme cases, those patients end up with severe complications, chronic and painful side effects, and may even die of GVHD.”

Dr. Kean noted that GVHD is one of the main reasons many bone marrow transplant patients endure long hospital stays after their diseases are cured. She said the new findings are exciting because the drug studied is in advanced clinical trials. “So, we are hopeful that bone marrow transplant recipients will benefit from this research in the near future,” said Dr. Kean.

The drug Dr. Kean’s lab worked with is very similar to one that is produced by the Takeda Pharmaceutical Company, and is in phase III clinical trials for pediatric and adult cancers. The drug inhibits the aurora kinase A signaling pathway, causing cells to stop dividing.

Study collaborator Ned Waller, MD, who is a Professor of Medicine, Pathology and Hematology/Oncology at Emory University in Atlanta, said this study represents the very best of team science. He noted that it was a hypothesis-driven, collaborative effort across multiple institutions, and is now immediately relevant to clinical patient care. Dr. Waller noted new approaches to understand the immunology of GVHD and limiting its impact are urgently needed to improve the quality of life for patients and increase their long-term, cancer-free survival.

Dr. Kean and her team hope to launch a clinical trial in 2016 to apply this new strategy so that patients undergoing bone marrow transplantation may have access to aurora kinase A inhibitors.