Whether fish, snakes or scorpions: Many animals use poisons to make prey or to defend themselves against enemies. These toxic weapons are also of increasing interest to medical professionals. Because some of their ingredients have therapeutic potential. Also for the treatment of arthritis, as can now be seen: Researchers have found a mini protein in the poison of scorpions that accumulates in cartilage tissue itself – in other words, where the joint inflammation takes place. Experiments with rats suggest that these substances can be used to deliver drugs to the joint in a targeted manner. This significantly reduces the risk of side effects.
Arthritis is a real common ailment: especially many older people suffer from this inflammatory joint disease, which causes severe pain and destroys the cartilage. Common treatment methods can alleviate the inflammation symptoms and slow down the breakdown of the protective cartilage layer in the joints. However, the drugs used for this, such as steroids, have one crucial disadvantage: they often work throughout the body and lead to a variety of side effects. “These are sometimes as bad or even worse for patients than the disease itself,” explains Jim Olson of the Fred Hutchinson Cancer Research Center in Seattle. Steroids and Co can therefore usually only be taken for a short time.
Targeted to cartilage
An optimal solution to this problem would be to bring the active ingredients specifically into the sick joints and thus protect the rest of the organism. But how can this be done? In search of an answer, Olson and his colleagues around first author Michelle Cook Sangar have now devoted themselves to a class of mini proteins that are found in the poison of many spiders, snakes and scorpions. These so-called cystine-dense peptides (CDPs) are characterized, among other things, by their disulfide bridges, which stabilize the peptide structure and give the proteins particular stability – an important property for a potential therapeutic effect. The researchers already knew that these substances produced by nature’s toxic mixers had medical potential. In a previous study, they found that some of these proteins bind specifically to tumor cells and – with their luminous properties – can help diagnose cancer.
For their current investigation, the scientists analyzed a total of 42 CDPs from 20 different animal species. They found that some of these peptides appear to accumulate specifically in cartilage tissue. When administered to rodents, they migrate specifically to the knees, hips, ankles and shoulders. The substances also bind to human cartilage tissue in the petri dish, as experiments revealed. Among other things, this could be due to the electrostatic properties of the peptides: their surface is mostly positively charged. “This seems to differentiate the cartilage-accumulating candidates from other CDPs,” the team reports.
Therapy test with rats
In a next step, the researchers took a closer look at a particularly promising drug candidate. The experiment with rats and mice showed that the miniprotein called CDP-11R reached its peak concentration in the cartilage 30 minutes after systemic administration, but was still detectable in the tissue after more than four days. This made it clear to Sangar and her colleagues that this substance contained in scorpion poison actually had potential for the treatment of inflammatory joint diseases. All he had to do was load it with the appropriate medication. “The idea sounds simple: you take a mini protein that immigrates into cartilage and binds something to it in order to achieve targeted drug administration. But it was a real challenge to actually get this done, ”reports co-author Emily Girard.
After the scientists finally succeeded, they did the practical test. They linked the steroid triamcinolone acetonide to the protein and used it to treat rats with rheumatoid arthritis for several days. The result: the product relieved the inflammation of the joints of the animals without affecting other tissues such as the thymus and spleen. These organs often suffer damage from undirected steroid administration, and even in the control experiment without the miniprotein, treatment with the same dose of active substance led to undesirable side effects in other parts of the body, as the team reports. These results show that a small protein from the poison of scorpions could make life easier for patients with arthritis in the future. But further research is needed first. It must be shown whether the miniprotein-steroid combination is effective and safe even with long-term use and which doses would be necessary for human patients.
Source: Michelle Cook Sangar (Fred Hutchinson Cancer Research Center, Seattle) et al., Science Translational Medicine, doi: 10.1126 / scitranslmed.aay1041