Scorpion Venom Toxin Reduces Severity of Rheumatoid Arthritis in Rats

Dr. Christine Beeton from Baylor College of Medicine and colleagues have found that iberiotoxin — one of the components in the venom of a scorpion species called the Eastern Indian red scorpion (Buthus tamulus) — can reduce disease severity in a rat model of rheumatoid arthritis.

The Eastern Indian red scorpion (Buthus tamulus) in Mangaon, Maharashtra, India. Image credit: Shantanu Kuveskar / CC BY-SA 4.0.

The Eastern Indian red scorpion (Buthus tamulus) in Mangaon, Maharashtra, India. Image credit: Shantanu Kuveskar / CC BY-SA 4.0.

“Rheumatoid arthritis is an autoimmune disease — one in which the immune system attacks its own body. In this case, it affects the joints,” Dr. Beeton said.

“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.”

Current treatments target the immune cells involved in the disease and none are specific for FLS.

Dr. Beeton and co-authors studied FLS looking for an ‘Achilles’ heel’ that would allow them to prevent or stop them from damaging the joints.

“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,” Dr. Beeton said.

“We wanted to find a way to block the channel to stop the cells damaging the joints.”

Potassium channels work by opening gates on the surface of cells that allow potassium ions to flow in and out of the cell. The flow of ions through the channels is necessary for the cells to carry out many of their essential functions.

Animals such as scorpions have venoms that block potassium and other ion channels. They use the venoms to paralyze and kill prey.

Decades ago, scientists discovered this and realized that, if handled correctly, venoms also might have medicinal applications.

“Iberiotoxin specifically blocks the potassium channel of FLS and not the channels in other cells such as those of the nervous system,” said Mark Tanner, also from Baylor College of Medicine.

“Here, we investigated whether 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.”

When the researchers treated rat models of the disease with iberiotoxin, they stopped the progression of the disease.

In some cases they reversed the signs of established disease, meaning that the animals had better joint mobility and less inflammation in their joints.

In addition, treatment with iberiotoxin did not induce side effects, such as tremors and incontinence, observed when treating with another channel blocker called 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,” Dr. Beeton said.

“We think that iberiotoxin can become the basis for developing a new treatment for rheumatoid arthritis in the future.”

The study was published online this month in the Journal of Pharmacology and Experimental Therapeutics.

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Mark R. Tanner et al. Targeting KCa1.1 channels with a scorpion venom peptide for the therapy of rat models of rheumatoid arthritis. Journal of Pharmacology and Experimental Therapeutics, published online February 16, 2018; doi: 10.1124/jpet.117.245118

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