They mightn't seem like the most obvious places to look, but the venom of deadly creatures like spiders, snakes and scorpions are an increasingly rich source of medicines for human health. The latest example of this comes from scientists at Fred Hutchinson Cancer Research Center, who have discovered a tiny protein in scorpion venom that could become part of a potent new treatment for arthritis.
While drugs exist to treat inflammation in sufferers of arthritis, a scattergun approach means that the often bring severe side effects. These types of non-targeted steroid treatments sweep through the whole body and while they can act swiftly to relieve inflammation, they can also cause high blood pressure or weight gain, and make it harder for diabetics to manage their condition, to list a few examples.
“For people with multijoint arthritis, the side effects of controlling the disease can be as bad or worse than the disease itself,” says Dr. Jim Olson, who led the new research. “Steroids like to go everywhere in the body except where they’re needed most. This is a strategy to improve arthritis relief with minimal systemic side effects.”
This strategy Olson speaks of is the product of more than a decade of toiling away in the lab, searching for proteins in scorpion venom that can be used as the basis for advanced drugs to treat various ailments. Around four years ago while screening dozens of peptides from the venom of scorpions and spiders, he and his team found one that seemed to naturally buildup in the cartilage.
This struck the scientists instantly as a potential way to develop more targeted treatments for arthritis. This led to years of trial and error and more tinkering in the lab, until the researchers came up with a recipe that appears to have the desired effect. It involved pairing this peptide with a steroid called triamcinolone acetonide, a combination that was then tested in rats where it proved capable of concentrating in the joints and reversing inflammation in rats with arthritis. And crucially, it produced no detectable side effects.
“It’s a pretty simple idea to take a mini-protein that naturally goes to cartilage and attach something to it so that you get targeted delivery of the drug, but it was challenging to accomplish,” said Emily Girard, a staff scientist in Olson’s lab. “We had to learn and adapt the behavior of the mini-protein, the chemical linker and the steroid payload to make a product that would go to cartilage, stay as long as we needed it to, release the drug at the right rate, and have a local but not systemic effect. There is more development to be done, but I hope that this work results in a therapeutic that will help a lot of people.”
The scientists note that the treatment is still years away from entering clinical use, but describe the proof of concept as "promising."
The team's research was published in the journal Science Translational Medicine.
