Biochemists at the University of Texas at Arlington have discovered a key to easing the dangerous side effects of certain drugs that can keep the body from rejecting transplanted organs and attacking its own joints as it does with rheumatoid arthritis.
The researchers focused on the thiopurine class of drugs that, while doing their intended work, can also cause side effects such as cardiovascular disease and hypertension.
“Up to now, no one has known exactly how the thiopurine immunosuppressive process works,” Jongyun Heo, associate professor of chemistry and leader of the study published in the Journal of Biological Chemistry, said in a news release. “We are hoping that this discovery also creates an opportunity to improve thiopurine drugs and to design new chemotherapeutic agents for autoimmune disorders.”
The research showed that thiopurine drugs create bonds that interfere with the function of a protein called Rac1 in the T cells — the building blocks of the body’s immune system. The disulfide bonds deactivate the protein and suppress the T cell’s immune response.
The research has turned up some other promising leads. Thiopurine drugs also can bond with two other proteins involved in vascular disease and cancer growth.
“It is now important to investigate whether thiopurine directly induces vascular or heart diseases through bonds with these other proteins, to alleviate potential cytotoxicities and side effects,” Heo said in the statement. “There is also a potential opportunity to take advantage of this knowledge to develop new tools to fight cancer by stopping cancer metastasis by inactivating the proteins involved in cell proliferation.”
Heo’s co-author on the paper was Jin-Young Shin of the Biologics Research Division of the National Institute of Food and Drug Safety Division of South Korea. A National Institutes of Health grant supported the work.
“Large numbers of patients dependent on thiopurine drugs could potentially benefit from improvements in the drug or new drugs developed on the basis of this discovery,” said Fred MacDonnell, chair of chemistry and biochemistry at UTA. “Further research could also help improve our tools in the fight against cancer, which would be another important step forward.”