Feel-Good News: Powerful Drug Combo Offers Potential Osteoarthritis Relief

SAN DIEGO — Two may be better than one, at least when it comes to fighting arthritis. Recent research at the Salk Gene Expression Laboratory has found that a combination of two osteoarthritis drugs is better than either one alone. In fact, researchers say the medicinal cocktail actually reversed signs of the condition in rats.

Osteoarthritis, known as “wear and tear” arthritis, causes joint stiffness and pain. Over time, the cartilage that cushions bones breaks down and there is overgrowth on the underlying bones. So far, pain relievers and joint replacement surgery are about the only remedies offered for the 30 million U.S. adults who have this disease.

But that may change with the powerful one-two punch drug combo currently being studied for potential use in humans.

Arthritis
The top image shows a knee joint in a healthy rat. (White indicates cartilage.) The second image from top shows a joint with grade 2 untreated osteoarthritis. The third image shows a joint with osteoarthritis that has worsened from grade 2 to grade 4 after six weeks of placebo therapy. The bottom image shows a joint with osteoarthritis that improved from grade 2 to grade 1 (mild) after six weeks of combination therapy with alphaKlotho and sTGFbR2. (Credit: Salk Institute)

Scientists considered two drugs that singly offered some degree of success in treating osteoarthritis in animal studies. The first drug, known as αKLOTHO, keeps the mesh of molecules surrounding articular cartilage cells strong and healthy. The other, TGFβR2, stimulates growth in the cartilage cells themselves.

They wondered what might happen if the two were combined. Scientists conducted experiments on rats and isolated human cartilage cells in a laboratory setting, and found that the two drugs together reverse cellular and molecular symptoms of osteoarthritis.

“What’s really exciting is that this is potentially a therapy that can be translated to the clinic quite easily,” says Juan Carlos Izpisua Belmonte, lead author and a professor at the Salk laboratory, in a news release.

Researchers divided two groups of young, otherwise healthy rats with osteoarthritis. The control group received a placebo, while the other group was given a viral treatment of particles with both αKLOTHO and TGFβR2 DNA.

After six weeks, rats in the placebo group had progressed from stage 2 to stage 4 osteoarthritis in their knees. Rats receiving the particles with the drug combination, however, improved from stage 2 to stage 1 (mild) osteoarthritis. In this group, scientists observed thicker cartilage, more cell growth and no negative side effects.

Additional experiments provided some clues about how the combination treatment works. In the treated rats, 136 genes became more active and 18 genes less active than in the placebo group. Many of these genes are connected to inflammation and immune responses.

Researchers next treated isolated human articular cartilage cells with the combination of αKLOTHO and TGFβR2. They found increases in molecules connected to cell growth and extra-cellular matrix development.

The study’s authors caution that the results are not necessarily indicative of what these drugs might accomplish in a human knee joint. They do believe, however, that there is great potential for future use in humans.

Next plans for the study team include investigating whether soluble molecules of αKLOTHO and TGFβR2 proteins can be given directly, without the use of viral particles as carriers. They also want to find out whether the combination of these two drugs could be used as a preventive treatment for osteoarthritis.

“We are excited to continue refining this promising combination therapy for human use,” concludes Izpisua Belmonte.

Study results are published in the journal Protein & Cell.

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