While aiming at developing rheumatoid arthritis therapies that result in minimal side effects, researchers at Washington University School of Medicine in St. Louis have genetically engineered cells that, when implanted in mice, will deliver a biologic drug in response to inflammation. 

Through a mouse model of rheumatoid arthritis, it was seen that these engineered cells reduced inflammation and saved from a damage to bone known as bone erosion. The research team aims to provide therapies to those coping with the debilitating rheumatoid arthritis. 

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“Doctors often treat patients who have rheumatoid arthritis with injections or infusions of anti-inflammatory biologic drugs, but those drugs can cause significant side effects when delivered long enough and at high enough doses to have beneficial effects,” said senior investigator Farshid Guilak, PhD, the Mildred B. Simon Professor of Orthopaedic Surgery. “We used CRISPR technology to reprogram the genes in stem cells. Then we created a small cartilage implant by seeding the cells on woven scaffolds, and we placed them under the skin of mice. The approach allows those cells to remain in the body for a long time and secrete a drug whenever there is a flare of inflammation.”

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The researchers used CRISPR-Cas9 genome editing technology to engineer cells that release a biologic drug in response to inflammation. It reduces inflammation in joints by attaching to interleukin-1 (IL-1), an inflammation-promoting substance. 

Guila and his team earlier developed scaffolding that they coat with stem cells to later implant into joints to form cartilage. His lab also previously built so-called SMART cartilage cells (Stem cells Modified for Autonomous Regenerative Therapy) using CRISPR-Cas9 technology.

In the new study, the combined these strategies to treat rheumatoid arthritis. 

“The cells sit under the skin or in a joint for months, and when they sense an inflammatory environment, they are programmed to release a biologic drug,” said Guilak. 

“We focused on bone erosion because that is a big problem for patients with rheumatoid arthritis, which is not effectively treated by current biologics” said co-first author Yunrak Choi, MD, a visiting orthopedic surgeon in the Guilak lab. “We used imaging techniques to closely examine bones in the animals, and we found that this approach prevented bone erosion. We’re very excited about this advance, which seems to meet an important unmet clinical need.”

Guilak also teamed up with Christine Pham, MD, director of the Division of Rheumatology and the Guy and Ella Mae Magness Professor of Medicine.

“Although biologics have revolutionized the treatment of inflammatory arthritis, the continuous administration of these drugs often leads to adverse events, including an increased risk of infection,” Pham explained. “The idea of delivering such drugs essentially on demand in response to arthritis flares is extremely attractive to those of us who work with arthritis patients, because the approach could limit the adverse effects that accompany continuous high-dose administration of these drugs.”

The experimentations are still going on with CRISPR-Cas9.