A team of researchers from Johns Hopkins conducted a study that revealed the removal of old or “senescent” cells from joints could reverse the progression of or prevent osteoarthritis.
The findings support increasing evidence that senescent cells are associated with osteoarthritis, an age-related disease, and signify that utilizing drug therapy to eliminate them creates a suitable environment for cartilage regeneration and repair, as well as decrease the development of post-traumatic osteoarthritis.
As we age, senescent cells collect in tissues and are a normal part of injury repair and wound healing. These cells produce signals that communicate with immune cells and other cell types, telling them to clean up and rebuild damaged tissue. However, in many cases senescent cells are not removed from articular joints like the knee and specifically cartilage tissue. The prolonged presence of senescent cells in joints brings about a cascade of events, beginning with the development of the age-related disease, osteoarthritis.
The research team cut anterior cruciate ligaments (ACL) to imitate injury in young mice. Fourteen days after trauma, an experimental drug called UBX0101, previously identified to eradicate senescent cell in laboratory studies, was then injected into the mice’s joints. At this point, degradation had already begun and senescent cells were already decreased by an estimated 50 percent. Researchers also monitored gene expression in the mice that had been treated with UBX0101 and discovered that after treatment the genes linked to reparative cartilage growth were activated in the joint.
Older mice were utilized in similar experiments as the younger mice. There were some crucial differences, including the older mice had increased pain levels prior to the experiment and much thinner cartilage in the joint. After UBX0101 injections, the older mice demonstrated decreased pain like their younger counterparts. However, the older mice did not demonstrate signs of new cartilage growth.
To determine the effectiveness of UBX0101 in humans, the research team utilized cultured cartilage cells from human donors, who have been diagnosed with severe osteoarthritis and/or undergone a total knee arthroplasty due to osteoarthritis. The cartilage cells were then grew into 3D structures – imitate how the cartilage tissues grow in the human body – in the lab and exposed them to the experimental drug, UBX0101, for four days. The findings revealed that the number of senescent cells was greatly decreased and the donor tissue started forming new cartilage after the senescent cells were eliminated.
The only downside to UBX0101 is it remains in the joint for only a short period of time. However, the co-developer of the drug, Unity Biotechnology, is currently working on single-injection formulations.
Director of the translational tissue engineering center and Morton Goldberg professor of Ophthalmology at the Johns Hopkins Wilmer Eye Institute, Jennifer Elisseeff, Ph.D., said, “Because the drug targets and kills senescent cells directly, once they are eliminated patients will not need to return for frequent treatments.”
The findings were published in the journal Nature Medicine on April 24, 2017.