Scorpion venom protein might be used to ferry drugs to the brain

Researchers have found a way to take advantage of one of venom’s most dangerous properties: its ability to reach the brain.

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The brain is the most complex human organ, and like any complex mechanism, it’s vulnerable to external interference. That’s why it’s hidden in our sturdy skulls, surrounded by cerebrospinal fluid, and locked tight by the blood-brain barrier (BBB). The blood-brain barrier is a highly selective semipermeable border that ensures no unwanted pathogens reach the brain.

However, all this protection comes at a cost: it’s really hard to for doctors to deliver necessary drugs to the brain, and sometimes, a drug has to be administered directly into the cerebrospinal fluid.

“About 98% of drugs that could have therapeutic applications cannot be used because they cannot cross this barrier,” explains Ernest Giralt one of the authors of the new study, and lab leader at the Institute for Research in Biomedicine Barcelona.

Giralt and colleagues may have found a workaround that issue, employing the usage of an unexpected substance: venom.

The venom of the Giant Yellow Israeli scorpion (Leiurus quinquestriatus), a species native to desert habitats ranging from North Africa through to the Middle East, could hold the key. The venom holds a small protein (a peptide) derived from chlorotoxin that has the ability to penetrate the blood-brain barrier.

“Our goal is to enable drugs to enter the brain and to do this we bind them to peptides specifically designed to cross the BBB. The conjugation of these drugs to the shuttles would improve their efficacy,” says Meritxell Teixidó, co-leader of the research.

Essentially, the venom could serve as a shuttle for drugs — which is not entirely a new idea. In previous studies, scientists took inspiration from a peptide found in bee venom (named apamin), making a few minor chemical modifications to ensure that it can pass the BBB. However, chlorotoxin, which is found in the venom of the scorpion, already has this ability — it’s one of the reasons why the scorpion’s venom is so dangerous. In other words, they took one of the threats of venom and found a way to use it as an advantage.

“Thousands of venoms that hold millions of peptides with the shuttle potential have been described. We chose chlorotoxin because it has already been reported that it acts like a toxin in the brain,” explains Teixidó.

So far, preliminary results are highly encouraging. Although this still needs to be investigated and thoroughly confirmed, it’s quite promising.

“Our results reveal animal venoms as an outstanding source of new families of BBB-shuttles,” researchers conclude.

The study “From venoms to BBB-shuttles. MiniCTX3: a molecular vector derived from scorpion venom” has been published in Chemical Communications.

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