Rheumatoid arthritis (RA) is an autoimmune disorder affecting over 2 million Americans. Those patients may eventually use a new kind of therapeutic, one made from scorpion venom. A team of investigators led by Dr. Christine Beeton at Baylor College of Medicine has determined that one component out of hundreds in scorpion venom can ease the symptoms of RA in animal models; there also weren't side effects like those seen with other treatments like this one. This work has been reported in the Journal of Pharmacology and Experimental Therapeutics.
"Rheumatoid arthritis is an autoimmune disease - one in which the immune system attacks its own body. In this case, it affects the joints," explained Beeton, associate professor of molecular physiology and biophysics and member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine. "Cells called fibroblast-like synoviocytes (FLS) play a major role in the disease. As they grow and move from joint to joint, they secrete products that damage the joints and attract immune cells that cause inflammation and pain. As damage progresses, the joints become enlarged and are unable to move."
Typical therapies act on the immune cells that are part of the disorder, but none of them are especially for treating FLS. Beeton's team wanted to find a weakness they could exploit so a better treatment for FLS could be created that halts or prevents joint damage.
"In previous work, we identified a potassium channel on FLS of patients with rheumatoid arthritis and found that the channel was very important for the development of the disease," Beeton said. "We wanted to find a way to block the channel to stop the cells damaging the joints."
The surface of cells have potassium channels that have gates controlling the movement of potassium ions in and out of the cell. That flow is critical to cellular function. Some animals carry compounds that block these ion channels; their venom exerts that effect, disabling and killing prey. Scientists have known for years that this mechanism might have medicinal uses.
"Scorpion venom has hundreds of different components. One of the components in the venom of the scorpion called Buthus tamulus specifically blocks the potassium channel of FLS and not the channels in other cells such as those of the nervous system," said the first author of the work Dr. Mark Tanner. "Here, we investigated whether this venom component, called iberiotoxin, would be able to specifically block the FLS potassium channel and reduce the severity of the rheumatoid arthritis in rat models of the disease."
In this study, a rat model of RA was used. After treatment with iberiotoxin, the disease progression was halted or in some cases, reversed; the animals showed a reduction in joint inflammation and better mobility. This treatment also didn't cause side effects that are seen with a similar drug, paxilline.
"It was very exciting to see that iberiotoxin is very specific for the potassium channel in FLS and that it did not seem to affect the channels in other types of cells, which might explain the lack of tremors and incontinence," Tanner said.
"Although these results are promising, much more research needs to be conducted before we can use scorpion venom components to treat rheumatoid arthritis," Beeton added. "We think that this venom component, iberiotoxin, can become the basis for developing a new treatment for rheumatoid arthritis in the future."