A team of scientists have recently found a method for a simple knee injection that could possibly halt the effects of this disease. The team was able to show that by targeting in mice a specific protein pathway then follow with putting it in overdrive, they could halt the degeneration of cartilage over time.
The team then built on this finding by illustrating that by treating mice who had surgically induced knee cartilage degeneration, through the identical pathway through state of the art nano-medicine, they could reduce the knee pain and degeneration of cartilage quite dramatically.
The team’s lab is just one of the few studying EGFR (epidermal growth factor receptor) signaling in cartilage. From their beginning, they have discovered that EGFR inactivation or deficiency speeds up the progression of osteoarthritis in mice. Therefore, they proposed that its activation might be utilized for osteoarthritis treatment. They have proven that over-activating it within the knee will block the progression of the disease.
Although the tests from a variety of other labs that also work with EGFR have shown controversial and confusing results, the current labs work has consistently shown ties between EGFR deficiencies and osteoarthritis which has formed the foundation of this team’s hypothesis.
The team compared regular mice with mice that contained a molecule that will bind to EGFR which is known as a ligand, that had been over-expressed in chondrocytes which are cartilage building blocks. The over-expression will drive the over-activation EGFR signaling that occurs in knee cartilage.
When the team examined the mice, they found that the mice with over-expressed EGFR ligand consistently had enlarged cartilage. This meant that the cartilage wasn’t deteriorating like the mice that had the normal EGFR activity. Additionally, as these mice entered adulthood, their cartilage was shown to be resistant to degeneration and a variety of other osteoarthritis hallmarks. This occurred even when the meniscus of their knee showed damage.
The team then went further to prove that the mice over-activated EGFR was the cause for the resiliency in these mice. They found that treatments called gefitnib which have been designed to block function of EFGR, removed the protection against degeneration of the cartilage.
Using all this knowledge, the team looked toward possible clinical treatments. Using a new variety of tests, they then created nano-therapeutics using a potent EGFR ligand to transform growth factor-alpha onto nano-particles in synthetic form, to inject into the mice who previously had damage to their knee’s cartilage.
EGFR ligands which are free only have a very short half-life and therefore can’t be retained inside a joint capsule because of their small size. Nanoparticles will help restrict them in the joint, offer protection from degradation, lessen off-target toxicity, and send them deep within dense cartilage in order to reach chondrocytes.
When the mice were given an injection of the nano-therapeutics, the team noted that they slowed down the degeneration of the cartilage and hardening of bone in addition to easing knee pain. They also noted there were no significant side effects experienced in the mice that were treated.
Although there are a lot of technical aspects the team’s application will need to be worked out, the ability to slow down or even stop the direction of osteoarthritis through an injection instead of surgery, would quite dramatically alter how we function and feel after injury and as we age.
Treatments are most likely in the distant future for humans, however the nano-particles that were used have been tested in the clinic and considered safe. This paves the way for quick translation to clinical use.
To view the original scientific study click below
Targeting cartilage EGFR pathway for osteoarthritis treatment.
