Osteoarthritis is a painful, debilitating and fairly common condition that’s hard to slow or stop, so treatment options are mostly limited to reducing pain. But a new study in mice has now found that nanotherapeutic injections into the knee can slow cartilage degradation.
Cartilage plays a key role in our joints, especially our knees, where it cushions against the forces of a lifetime of walking and running. But because it doesn’t naturally repair itself, the tissue can degrade over time or due to injury, leading to the pain associated with osteoarthritis.
In recent years, scientists have found ways to potentially slow the degradation of cartilage using a molecule derived from algae, or even regrow it by tweaking stem cells or injecting certain molecules. In the new study, the researchers developed their own molecule that shows promise in regenerating cartilage, by targeting a protein pathway previously linked to cartilage growth.
“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,” says Ling Qin, co-corresponding author of the study. “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.”
First, the team confirmed the link by engineering mice with overactivation of EGFR. These animals had enlarged cartilage that didn’t wear away as easily over time like that in control mice, and even resisted damage when the team surgically removed some of their meniscus to mimic osteoarthritis. The inverse was also tested – mice that were given a drug that blocked EGFR function had accelerated cartilage degeneration.
Next, the researchers created new nanotherapeutics based on this pathway. They attached an EGFR ligand called transforming growth factor-alpha (tgf-α) to synthetic nanoparticles, which could be injected into the knee to slow cartilage degeneration.
“Free EGFR ligands have a short half-life and cannot be retained inside of a joint capsule due to their small size,” says Zhiliang Cheng, co-corresponding authors of the study. “Nanoparticles help to protect them from degradation, restrict them within the joint, reduce off-target toxicity, and carry them deep inside dense cartilage to reach chondrocytes.”
The team tested the treatment on mice with cartilage damage, and found that cartilage degeneration and bone hardening slowed down, and their knee pain seemed to ease. No major side effects were noted, either.
As promising as the results sound, there’s still plenty of work to do in animal tests before it could ever move to human trials. But, the team notes, the nanoparticles themselves have already been clinically tested with positive results, so that part at least could be streamlined.
“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,” says Jaimo Ahn, co-author of the study.
The research was published in the journal Science Translational Medicine.
Source: University of Pennsylvania
