Scorpion venom mini-proteins in RA treatment
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The next new treatment for rheumatoid arthritis could come from the unlikeliest of sources. Researchers based at Seattle Children’s Hospital spent the last several years studying the potential use of mini-proteins found in scorpion venom toxin — not to poison, but to help heal.
The proteins already yielded positive effects though several clinical trials in the treatment of brain cancer, and their unique properties gave lead researcher Jim Olson, MD, PhD, principal investigator at Ben Towne Center for Childhood Cancer Research, in Seattle, a hunch. He wondered if these fast-moving, fast-acting proteins could help RA drugs get to affected joints more efficiently.
“My idea was that if these things are being used in nature for predation and defense, they need to be fast-acting; they need to get unique places in the body; and they probably have some very unique properties,” Olson said. “On a whim, we said ‘Let's make a few dozen and test them out.’ It was a surprise to us when we saw the joints lighting up, a very pleasant and unexpected surprise. Sometimes you make a left turn in your research when you see something like that.”
Olson and colleagues found that scorpion venom proteins work well as a conveyance mechanism and could potentially help mitigate the adverse effects of steroids on patients with RA.
“The steroids are wonderful, because we could relieve the pain, we could relieve the symptoms,” Olson said. “But what if we could actually halt the progress of arthritis and turn back the machinery that causes arthritis in the joints? Our next 5 years is going to be focused on payloads, other than steroids, that could affect progression of the disease.”
A modern approach to an old concept
Olson and his team are far from the first to examine plants and animals for potential medical use in humans. But he’s had a unique journey to arrive at these discoveries. He started from a crowdfunding campaign that eventually raised millions of dollars to allow his team to create new robotic systems from scratch and took a new view on an old area of study.
“Every plant and animal needs to defend itself,” Olson said. “They get sick and they can’t go to Walgreens. And so they need to come up with their own drugs. And in some cases, they’re just chemical drugs that are made and then disappear. But in other cases, they’re encoded in the DNA, and they get passed from parents to offspring. And those that make the best drugs are the ones that have the best survival advantage through evolution. Nature has been improving and honing these drugs for millions of years.”
Olson found ways to streamline these processes with a technology-forward approach, building upon past research on animal genomes to quickly sift through thousands of potential candidates to find specific traits.
“In the past, people would discover these drugs by taping a scorpion to their laboratory benchtop and touching its tail with an electrode, and a drop of venom would come out,” Olson said. “Then they would take that drop of venom and try to isolate one specific molecule out of it and then characterize that molecule. But it’s extraordinarily time-consuming. I don’t want to have scorpions taped to my desk. And all the other scientists in the world had together come up with about 2,000 of these mini proteins from animals and plants over the course of maybe 40, 50 years. We decided to take a more modern approach. We wrote a Python program that went through all the genomic databases in the world, and we identified about 80,000 more of them in a day and a half.”
A potentially revolutionary treatment
The speed and efficiency with which these proteins can reach affected joints allowed Olson to envision the role they would play in RA treatment, and the potential impact they might have.
“The treatment that we envision would be something that a patient would give themselves through subcutaneous injection maybe once a week,” Olson said. “And the goal would be to halt arthritis progression, or even reverse the disease process so that the joint recovers. Ideally, we would catch arthritis in early stages, use this until the arthritic processes were shut down and eliminate the need for sometimes toxic and ineffective medicines that are currently being used to treat arthritis.”
Studies continue into how they can be used to treat RA and other medical conditions, and Olson has recently collaborated with rheumatologist Jane Buckner, MD, president of the Benaroya Research Institute at Virginia Mason, to find ways to apply the proteins to pathways that can directly treat RA.
“We identified several of these pathways,” Olson said. “In some cases, they’re already small molecules that block these pathways, but they don't get into the joints very well. We’re linking those small molecules to our delivery agent to see if we can get it in there. And in other cases, we're seeing if we can make many proteins that block the disease pathways.”
Widespread possibilities
Olson sees this area of study as extending beyond just RA.
His team is working on proteins that can help kill cancer cells, as well as more simple anti-inflammatory treatments. Their mix of maneuverability and specificity, he hopes, could be a game-changer.
“Many proteins from nature are what we call ‘mid-size medicines’,” Olson said. “You have antibodies, which are huge, they can be very specific, but they can't get to a lot of places in the body. Then you have small molecules that are very tiny, and they can get to a lot of places in the body. But a lot of times they don't have high specificity. These mid-size proteins can get to really cool places in the body, but you can also tune them to be as specific as antibodies. I think that there's enormous possibilities.”
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