Patients with rheumatoid arthritis have taken for decades a drug that also resulted in unwanted bone loss. But a researcher at Georgia Health Sciences University is studying a protein that could not only treat the disease but aid in bone growth.
Dr. Nianlan Yang, a post-doctoral fellow at GHSU, was recently awarded a two-year, $100,000 fellowship grant by the Arthritis Foundation. She is studying a component from a class of drugs called glucocorticoids, which includes the steroid prednisone.
The drugs have been used for many years to treat conditions such as rheumatoid arthritis even though how exactly they work in the body is not known, Yang said. The drugs have anti-inflammatory effects which are beneficial but can also have serious side effects, such as bone or muscle weakness or metabolic impacts that can bring on diabetes, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
The drug “just works on too many things,” Yang said. “It covers too much. So sometimes it will benefit you and sometimes it does some bad things to your body.”
The work began with just trying to understand the mechanisms of the drug.
“At first we’re just trying to figure out how glucocorticoid works,” Yang said. The research zeroed in on a protein called glucocorticoid-induced leucine zipper that appeared to be the way the drug was inhibiting inflammation. By that inhibition, it was also promoting stem cells to become bone-forming cells and promote bone growth.
“This is really interesting because most people believe glucocorticoids cause bone loss,” Yang said.
Some of her work will be in a mouse specially bred to overexpress the inflammatory agent to see whether the protein can block its effects but she would also like to create her own mouse model that overexpresses the GILZ protein. The goal is to continue to study the protein to find out what is causing the good effects, Yang said.
“We still need to find out which part can be used for drug development,” she said. “From (lab) bench to bed, that’s always a long way to go.”
The protein or small molecule could offer a way to have a double beneficial effect for rheumatoid arthritis patients.
“We have to look at how this inflammation triggered bone loss,” Yang said. “That’s why we’re interested in this small molecule because this small molecule can target both sides of this disease, inflammation and bone loss.”