Research finds that a new OA drug is able to kill old cells.
Osteoarthritis (OA) is a type of arthritis that occurs when cartilage at the ends of bones wears down. It can affect any joint in the body, but it most commonly affects the hands, neck, lower back, knees, and hips.
In people over the age of 60, OA occurs in 10 percent of men and 13 percent of women.
OA can develop due to general wear and tear on tissues from years of use, and therefore, risk increases as we age. However, the condition can also be caused by injury or surgical intervention.
Because the average age of the population is steadily increasing and due to the rise in obesity levels, OA cases are increasing in line.
Current treatments can help patients to manage their symptoms, but the underlying processes can not be reversed. A recent study, published in Nature Medicine, investigates whether a drug that removes senescent, or old, cells from the joint might be useful in the treatment of OA.
Senescent cells key to OA drug
Senescent cells naturally build up in our bodies as we age. They are a normal part of injury repair and wound healing. By secreting certain signals, various cell types are alerted and migrate to the damaged region to begin repairs.
Unfortunately, senescent cells in joints are not always cleared from the area once the injury is repaired. By staying well beyond their welcome, the senescent cells trigger a "cascade of events," culminating in the development of OA.
One of the researchers in the current study was Jennifer Elisseeff, Ph.D., director of the Translational Tissue Engineering Center and Morton Goldberg Professor of Ophthalmology at the Johns Hopkins Wilmer Eye Institute in Baltimore, MD. She says: "Combine age-related increases in senescent cells, plus trauma, and it's a double whammy."
For the study, the team first performed surgery on young mice: they cut their anterior cruciate ligaments, mimicking an injury.
Fourteen days later, once osteoarthritic changes were under way, they injected a drug into the mice's joints. The drug, snappily named UBX0101, has been shown to specifically kill senescent cells.
The team found that the mice that received UBX0101 had a 50 percent reduction in senescent cells.
As a double check, the team monitored gene expression in the mice following UBX0101 treatment, and the genes associated with cartilage growth were shown to be activated in the joint.
Following on from the experiments on younger mice, the team carried out similar trials on older mice. The older mice had thinner cartilage than the younger mice, and they also had increased levels of pain at the beginning of the experiment. Once they had been injected with UBX0101, they had a reduction in pain, but they did not show the same signs of cartilage regeneration.
UBX0101 in human tissue
Of course, the next step was to observe whether UBX0101 could have a similar effect on human tissue. The researchers therefore tested the drug on cultures of cartilage cells, taken from people with severe OA. These cultures were then grown into 3-D structures to mimic how the tissue grows in vivo.
After 4 days of exposure to UBX0101, the number of senescent cells was significantly reduced and, importantly, new cartilage began to form.
'What was most striking about the results in human tissue is the fact that removal of senescent cells had a profound effect on tissue from very advanced osteoarthritis patients, suggesting that even patients with advanced disease could benefit."
Jennifer Elisseeff, Ph.D.
The results were impressive and the drug shows real promise. Currently, however, there is a stumbling block: UBX0101 does not spend much time in the joint. In an attempt to cross this bridge, Unity Biotechnology, who helped to develop the drug, are "working on single-injection formulations."
This could, one day, mean that patients would need just one dose of treatment for OA. As Elisseeff explains: "Because the drug targets and kills the senescent cells directly, once they are eliminated, patients will not need to return for frequent treatments."
There is still a lot of ground to cover before this type of treatment is available, but it certainly offers a healthy portion of hope.