Tackling Arthritis Using Novel Immune System Modifying Tools

Arthritis is a common joint disease affecting 22.7% of the adult population in the United States. While osteoarthritis is the most common form of arthritis, rheumatoid arthritis (RA), an autoimmune disorder, affects over 1.3 million Americans from varying ethnic backgrounds. It is an aggressive form of arthritis where the body’s immune system attacks its own cells causing inflammation and painful swelling of multiple joints leading to damage and erosion of bone and cartilage.

Dr. Marxa Figueiredo, associate professor of Basic Medical Sciences in the Purdue University College of Veterinary Medicine, investigates novel approaches to reducing inflammation & bone loss due to arthritis, as well as enhancing bone repair. Funded by multi-million dollar grants from the National Institutes of Health (NIH), her research aims to develop new therapeutics that stimulate the body’s immune system to promote healing of rheumatoid arthritis (RA).

Dr. Figueiredo’s long-term goal is to develop a drug that can heal RA rather than manage symptoms for life. “Current therapies can effectively control the inflammation for this disease however cannot reverse the bone loss,” said Dr. Figueiredo. “New lines of therapies are emerging that can target the immune component of the disease, however, they are very expensive and still cannot promote bone or cartilage repair.”

Dr. Figueiredo’s lab is currently working on a new gene therapy to treat RA that aims to deliver a targeted form of the interleukin-27 (IL-27) protein. “This protein can rebalance different biological factors in the joint environment to control inflammation and promote bone repair,” Dr. Figueiredo said.

Two types of cells determine the daily maintenance of bone tissue. According to Dr. Figueiredo, removal of small amounts of bone mineral, a process called resorption, is facilitated by cells called osteoclasts.  This removal is balanced by deposition of new mineral by osteoblasts. The balance between these two cell types determines whether bone is made, maintained or lost. Inflammatory activity of cells like T helper 17 (Th17), though beneficial during an infection cycle, is associated with many autoimmune disorders, including arthritis, when the regulation of these cells is out of balance.  IL-27 is a cytokine or cell signaling protein that regulates immune cell and bone cell balance and suppresses the activity of inflammation-causing cells like Th17. The new gene therapy under development delivers IL-27 DNA into the muscle surrounding the joint and allows expression of targeted forms of IL-27 protein, with the goal of reducing inflammation and allowing bone to heal.  

For Dr. Figueiredo, working at Purdue University is a dream come true.  West Lafayette, Ind., was her childhood home, as her parents came to Purdue to pursue graduate studies when she was less than six months old. She later returned to Brazil with her parents after they earned their master’s degrees. “It was my dream to come back to Purdue and I feel very grateful to be here,” said Dr. Figueiredo. “I really enjoy being a part of the drug discovery efforts and collaborations available to our lab here at Purdue.”

Dr. Figueiredo is currently collaborating with Dr. Herman O. Sintim, drug discovery professor of chemistry at Purdue, on using small molecules to reduce inflammation and promote conversion of stem cells into cartilage. “Cartilage is a tissue that is particularly challenging to repair,” Dr. Figueiredo said. Additionally, she is working with two of her colleagues in the Department of Basic Medical Sciences, Associate Professor Russell Main and Assistant Professor Dianne Little, on models of osteoarthritis.

Dr. Figueiredo is proud to be a part of a college that constantly strives for and succeeds at increasing diversity among its students and faculty through strong mentorship and outreach efforts.  “The environment at PVM is very supportive. People here help each other out. In this environment I am able to better balance the key roles I have in my family and my research program without having to forego one for the other,” Dr. Figueiredo said. “I want to do my best to be a good role model to under-represented young scientists who are considering research careers in biomedical sciences.”