Nanotherapy of osteoarthritis
There is currently no cure for osteoarthritis, but a group of researchers from the University of Pennsylvania School of Medicine has discovered a method by which a simple injection into the knee joint can potentially stop the progression of the disease. Researchers have shown that if you act on a specific protein pathway and restart it, you can stop the degeneration of cartilage over time. Treatment of mice with the new method significantly reduced degenerative changes and pain in the knee joint.
The authors studied the transmission of signals of the epidermal growth factor receptor (EGFR) in cartilage, and found that the deficiency or absence of EGFR accelerates the progression of osteoarthritis in mice. They suggested that its activation could be used to treat osteoarthritis.
To test the hypothesis, the researchers compared normal mice with mice in which the HBEGF ligand associated with EGFR was overexpressed in chondrocytes, the building blocks of cartilage. This overexpression led to activation of EGFR signaling in knee cartilage. It was found that in mice with overexpression of HBEGF, the mass of cartilage tissue is constantly increasing, which means that it is not erased, as in mice with normal EGFR activity. Moreover, when these mice became adults, their cartilage was resistant to degeneration and other signs of osteoarthritis, even if the meniscus was damaged in the knee joint.
To prove once again that over-activated EGFR was associated with the resistance of mice to osteoarthritis, the researchers introduced the drug gefitinib, which blocks the function of EFGR and noted the loss of cartilage resistance to degeneration.
With all this knowledge, the researchers began to search for solutions for clinical use. In a series of tests, they created a nanotherapeutic drug by attaching a powerful HBEGF ligand to synthetic nanoparticles. Free HBEGF has a short half-life and cannot be held inside the joint bag. Nanoparticles prevent its degradation, detain it inside the joint, reducing toxicity to neighboring tissues, and deliver it deep inside dense cartilage to chondrocytes.
When the mouse models with osteoarthritis were injected with a new drug, the processes of cartilage degeneration slowed down, the pain in the knees decreased. No serious side effects were noted.
The nanoparticles that were used in the study have already passed clinical trials and are recognized as safe for humans. The design of the drug will be finalized and must be tested on large animals before it is admitted to clinical trials.
In addition, many technical aspects of the new treatment have yet to be improved.
The ability to stop or slow down the course of osteoarthritis by injection, rather than surgery, will help improve the well-being of patients with degenerative diseases of the knee joint.
Article Y.Wei et al. Targeting cartilage EGFR pathway for osteoarthritis treatment is published in the journal Science Translational Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to EurekAlert: Target discovered that halts osteoarthritis-type knee cartage degeneration.