New Target Discovered That Stops Progress of Osteoarthritis

Currently there is no cure osteoarthritis. A group of scientists have discovered a new method by which a simple knee injection can potentially stop the disease's effects. The researchers showed that by targeting specific protein pathway in mice, they can be put into overdrive and halt the cartilage degeneration over time. Using these findings, they were able to show that by treating mice with surgery-induced knee cartilage degeneration through nanomedicine could dramatically reduce the cartilage degeneration and knee pain.

The study conducted by Penn Engineering is published in the journal Science Translational Medicine.

Ling Qin, PhD, an associate professor of Orthopaedic Surgery said, “Our lab is one of the few in the world studying epidermal growth factor receptor (EGFR) signaling in cartilage and, from the beginning, we have found that EGFR deficiency or inactivation accelerates osteoarthritis progression in mice. Thus, we proposed that its activation could be used to treat osteoarthritis, and in this study, we've proven for the first time that over-activating it inside the knee blocks the progression of osteoarthritis.”

The researchers explained that tests conducted by other labs that do work with EGFR have drawn ‘confusing and controversial’ results. Qin’s lab has always found ties between osteoarthritis and EGFR deficiencies, which formed the bases of their hypothesis.

The researchers compared mice which had a molecule that bound to EGFR, called a ligand that was overexpressed in chondrocytes, the building blocks of cartilage. The over-activation of EGFR signaling in knee cartilage is driven by the overexpression of this molecule.

On examining the mice with overexpressed HBEGF (the EGFR ligand), it was found that they have consistently enlarged cartilage, meaning that it wasn't wearing away like the mice who had normal EGFR activity. Additionally, it was found that when these mice aged to adulthood, their cartilage was resistant to degeneration and other hallmarks of osteoarthritis, even if their knee's meniscus was damaged.

The researchers found that gefitinib treatments that are designed to block EFGR function, took away the protection against cartilage degeneration. This further proved that the over-activated EGFR was the reason for the mice's resiliency.

Treatment Options

To search for potential clinical treatment solutions, the researchers created nanotherapeutics by attaching a potent EGFR ligand, transforming growth factor-alpha, onto synthetic nanoparticles, to inject into mice that already had cartilage damage in their knees.

The researchers explained that the free EGFR ligands have a short half-life and cannot be retained inside of a joint capsule due to their small size. The nanoparticles help to protect to the ligands from degradation, restrict them within the joint, reduce off-target toxicity, and carry them deep inside dense cartilage to reach chondrocytes.

On injection of nanotherapeutics, mice showed slowing of cartilage degeneration and bone hardening, as well as eased knee pain. No major side effects were seen.

One of the co-authors of the study Jaimo Ahn, MD, PhD, associate chair of orthopaedic surgery at the University of Michigan said, “While many of the technical aspects of this application still need to be worked out, the ability to stop or slow the course of osteoarthritis with an injection rather than surgery would dramatically change how we feel and function as we age and after injury.”

As the nanoparticles have already been clinically tested and deemed safe, this makes it easier for its translation to clinical use.

Qin said, “There is a great unmet medical need for a disease-modifying osteoarthritis drug. In the future, we will optimize the drug design and test it in large animals before proceeding to clinical trials. We hope our research could lead to a novel drug that will improve the health and well-being of the more than 27 million osteoarthritis patients in the United States.”

Source-Medindia