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Scorpion venom might be an answer to treating arthritis - here's how it works

Scorpion venom could one day be used to manage arthritis symptoms, according to new research by scientists at the Fred Hutchinson Cancer Research Center and published recently in the journal Science Translational Medicine.

Source: Hutch News Stories, https://www.fredhutch.org/en/news/center-news/2020/03/scorpion-venom-arthritis-treatment.html

The cartilage-accumulating scorpion toxin was identified by Fred Hutch scientists through research that involved screening dozens of peptides derived from scorpions and spiders.

More than 24 million US adults are limited in their activities from arthritis,and more than 1 in 4 adults with arthritis report dealing with severe joint pain caused by multi-joint inflammation. There are existing therapies that can help relieve the pain of chronic arthritis, but many of those treatments come with significant side effects. For instance, although the use of strong steroids can effectively decrease joint inflammation, they also cause significant damage and toxicities to other tissues and systems in the body.  Dr Jim Olson, senior scientist at , US,

“For people with multi-joint arthritis, the side effects of controlling the disease can be as bad or worse than the disease itself. Steroids like to go everywhere in the body except where they’re needed most. This [current scorpion venom research] is a strategy to improve arthritis relief with minimal systemic side effects.”

A 'safer way' to treat arthritis

Scientists isolated a specific protein present in scorpion venom that rapidly accumulates in joint cartilages of the body, including the knees, ankles, hips, shoulders and spinal discs. In mice studies, researches were able to combine these proteins, known as cystine-dense peptides (CDPs),with a steroid normally used to treat rheumatoid arthritis to create a ‘drug delivery system’ that targeted only the joints and not the rest of the body. The tiny CDP scorpion protein basically carried the steroid directly to the joints only, and limited the amount of steroid exposure to other body tissues. They found that this novel drug delivery option reversed arthritis joint inflammation in the rodents, while avoiding steroid damage to other parts of the body.

Therapeutic, scorpion venom–derived peptides accumulate in mouse knee joint cartilage. The white box in the second column is imaged at 20x in the third column and showing peptides in red. SCIENCE TRANSLATIONAL MEDICINE (2020) Source: The Scientist

The current study looked at the effectiveness of treating Rheumatoid Arthritis in mice. In rheumatoid arthritis, the body's immune system targets affected joints, which leads to pain and swelling. After isolating the specific scorpion venom protein (CDP) capable of traveling quickly to joints, scientists then attached these proteins to triamcinolone acetonide (a commonly used steroid)and found that it helped concentrate the steroid drug within the cartilage of joints in rats with rheumatoid arthritis. The treatment reversed inflammation in the joints without damaging other tissues commonly affected by long-term or repeated steroid treatments.

The team plans future human clinical trials and hopes that these findings will one day offer arthritis sufferers effective ‘joint-specific’ treatment that avoids some of the systemic side effects of current medications including weakening of the bones, high blood pressure and increased risk of infections (a key limitation to administering steroids for long periods of time).

Related Video: What Is Arthritis?, Dr. Cory Calendine, MD

"...the value of playing scientifically..."

Discovery of a scorpion venom protein with a homing-system for joint cartilage was a surprise but not a random accident for Dr. James Olson. More than a decade ago, Olson discovered a mini-protein found in the deathstalker scorpion that can bind to cancer cells but not healthy ones. He then co-founded a company, Blaze Bioscience, that has developed an experimental dye called Tumor Paint BLZ-100 made from a special, glowing version of the deathstalker’s targeting protein. It is now being tested to one day allow surgeons to precisely illuminate hard-to-see brain tumors.

The Deathstalker scorpion is straw yellow in color and can grow 3.5 to 4.5 inches in length.

After Blaze BioScience was formed, Olson wondered what other potential drugs might be lurking in nature, and he continued his research with mini-proteins derived from natural organisms such as scorpions, snakes, violets and sunflowers.

“My thought was that these peptides that are in venoms or toxins might have really unique biodistribution in human bodies,” Olson said. “If something is using them for predation, they need to get to certain places rapidly.”

Four years ago, Olson and his team were investigating several peptides derived from scorpions and spiders, searching for molecules that could also cross the blood-brain barrier (the protective barrier is designed to keep most everything out of the brain). During those experiments they discovered one particular peptide that appeared to accumulate and linger in cartilage, and they quickly realized this could be a treatment for arthritis. 

“It really shows the value of playing scientifically and just doing things for the pure joy of learning,” Olson said. “You never know where it’s going to take you. If we could relieve arthritis for millions of people with very few side effects, that’s a really good investment of our time.”

Research Continues

James Olson, M.D., Ph.D. Professor, Clinical Research Division, Fred Hutch, Jennifer Lynn Kranz, Unravel Pediatric Cancer Endowed Chair

Further studies will continue to assess the safety of this method in animals over longer periods of time before moving on to human clinical trials, but this innovative technique of delivering therapeutic medications directly to joints while minimizing ‘whole-body’ exposure offers hope to arthritis patients.

“Development of a safe and effective targeting agent that can deliver a variety of systemically administered therapeutics to all joints throughout the body would be groundbreaking for the fields of orthopedics and rheumatology,”

If human trials are successful, on-target drug delivery that minimizes off-tissue damage could reduce arthritis symptoms or reverse the damage of arthritic diseases in millions of patients suffering with pain and limited physical mobility. Olson added that while this study involved steroids, it also establishes that these mini-proteins could potentially be used to deliver other drugs into cartilage.

“We think that steroids have important potential as a candidate for clinical development and we’re actively exploring other payloads that could be delivered to the joints,” Olson explains. “The long-term goal is to deliver molecules that go beyond controlling arthritis to actually reversing it.”
Related Posts: Top 6 Arthritis Myths Busted
Source: Fred Hutichinson Cancer Research Center, https://www.fredhutch.org/en/news/center-news/2020/03/scorpion-venom-arthritis-treatment.html
Research Article: "A potent peptide-steroid conjugate accumulates in cartilage and reverses arthritis without evidence of systemic corticosteroid exposure", Michelle L. Cook Sangar, Emily J. Girard,Gene Hopping, Chunfeng Yin, Fiona Pakiam, Mi-Youn Brusniak, Elizabeth Nguyen, Raymond Ruff, Mesfin M. Gewe, Kelly Byrnes-Blake, Natalie W. Nairn, Dennis M. Miller, Christopher Mehlin, Andrew D. Strand, Andrew J. Mhyre, Colin E. Correnti, Roland K. Strong, Julian A. Simon, James M. Olson, Science Translational Medicine  04 Mar 2020: Vol. 12, Issue 533, eaay1041, DOI: 10.1126/scitranslmed.aay1041

According to the Hutch News Stories, research was supported by the National Cancer Institute, Blaze Bioscience, and philanthropic funding from Project Violet, the Wissner-Slivka Foundation, the Kismet Foundation, the Sarah M. Hughes Foundation, Strong4Sam, Yahn Bernier and Beth McCaw, Len and Norma Klorfine, Anne Croco and Pocket Full of Hope.

Infographic showing how a future treatment of arthritis could involve using a scorpion-derived miniprotein (a peptide) that delivers arthritis drugs directly to joint cartilage. The approach could potentially improve the safety of arthritis treatment.  [Fred Hutchinson Cancer Research Center] PDF

Key words: cartilage, venom, research, arthritis, steroids, scorpion, treatment, rheumatology, orthopedics, joint, pain, inflammation

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Cory Calendine, MD is an Orthopaedic Surgeon and founding partner of the Bone and Joint Institute of Tennessee at Williamson County Hospital in Franklin, TN. Dr. Calendine is an expert in Joint Replacement, specializing in Hip and Knee Surgery. From diagnosis through treatment, the Orthopaedic Surgical experts at the Bone and Joint Institute use the latest techniques and technology to improve care for people with musculoskeletal problems. For more information, please contact our office or schedule your appointment today.  

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