Scientists have found that the combination of two experimental osteoarthritis medications greatly reduces arthritis in rats.
The team at La Jolla, CA’s Salk Institute for Biological Studies has also found that the drugs work on isolated human cartilage cells.
The results of this latest research will now appear in the Protein & Cell journal.
Osteoarthritis, or’ wear and tear ‘ arthritis, typically occurs in a person’s hands, thighs, or knees, according to the Centers for Disease Control and Prevention (CDC).
Osteoarthritis causes the cartilage to break down between the bones and the bones themselves to change their shape, leading to pain, stiffness and swelling in and around the joints.
Osteoarthritis in the United States affects more than 30 million adults. It is the main cause of disability in the U.S., because of the discomfort people associate with the disorder, according to an article in the journal Bone Research.
There is currently no remedy for osteoarthritis, but doctors usually treat the symptoms with pain medication, increased physical activity, weight loss, supportive aids such as crutches, and surgery where necessary.
The scientists at the Salk Institute noted that the ability of the body to fight wear and tear damage degeneration on the joints decreases with age and that very young mammals ‘ joints often have far better regenerative properties.
This led them to speculate whether treatment could be developed that encouraged these regenerative properties in the joints of older mammals.
The molecules alpha-KLOTHO (aKLOTHO) and TGF beta receptor 2 (TGFβR2) have been proposed as potential medicines for the treatment of osteoarthritis through prior research.
AKLOTHO affects the molecules surrounding cartilage cells, helping to stop the breakdown of this protective network, while TGFβR2 specifically inhibits cartilage cells, prevents them from breaking down and allows them to yield more cells.
In animal models every drug has had some success in preventing osteoarthritis. The output, however, had been modest. The Salk Institute team was curious if the combination of these two drugs would produce better results.
“We thought we could perhaps make something better by combining these two molecules that work in different ways,” says Paloma Martinez-Redondo, a postdoctoral fellow in Salk and co-first author of the new study.
An effective treatment for Arthritis
The researchers provided the rats with osteoarthritis the DNA instructions for making the two forms of molecules through the use of a harmless virus, while another group of rats obtained control particles.
The rats who got the control particles had more serious osteoarthritis in their knees after 6 weeks. In addition, the disease had shifted osteoarthritis from stage 2 to stage 4.
In contrast, the rats had considerably less arthritis with the combination of aKLOTHO and TGFβR2.
They had thicker, healthier cartilage, fewer cartilage cells were dying, and there were more cartilage cells that were actively proliferating. For these rats, their arthritis reduced from stage 2 to stage 1.
“We have seen a huge improvement from the very first time that we tested this drug combination on just a few animals,” says Isabel Guillen-Guillen, the co-first author of the paper. “We kept examining more animals and seeing the same positive results.”
After closer inspection, the scientists found that the drug combination influenced inflammation-related genes and immune responses, providing them information to help them understand exactly how the treatment worked and what areas to examine in the future.
Human arthritis
While the team performed these initial rat studies, experiments on isolated human cartilage cells were also conducted to see if the findings in humans could be replicable.
The researchers have found that the number of molecules they may correlate with making the cartilage healthier increased after treating the cells with the drug combination.
“It’s not the same as seeing how these drugs affect the knee joint in humans but we think it’s a good indication that this might work for patients,” says Martinez-Redondo.
The team plans to develop the work in two ways. First, they plan to investigate whether, rather than through a viral host, the drugs can be distributed in a soluble form.
Second, the team wants to see if the combination of the drugs could be effective in preventing osteoarthritis before symptoms worsen.
If so, this could open the door to a potentially far more successful human treatment option.
“We think that this could be a viable treatment for osteoarthritis in humans.”
– Pedro Guillen, co-corresponding author
