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November 22, 2018

Scorpion venom could hold the key to breaching the blood-brain barrier

The Peptides and Proteins Lab at the Institute for Research in Biomedicine has discovered the capacity of a small protein, found in scorpion venom, to carry drugs across the blood–brain barrier.

By GBI Research

The Peptides and Proteins Lab at the Institute for Research in Biomedicine (IRB Barcelona) has published a paper in Chemical Communications describing the capacity of a small protein (a peptide) derived from chlorotoxin, found in scorpion venom (Giant Yellow Israeli scorpion), to carry drugs across the blood–brain barrier (BBB).

This highly selective barrier serves to protect the brain from toxic substances, but also prevents many potential drugs from reaching the brain, contributing to the difficulty of treating neurological diseases and brain tumours.

“About 98% of drugs that could have therapeutic applications cannot be used because they cannot cross this barrier,” explains laboratory head, Ernest Giralt.

The researchers chemically synthesised chlorotoxin, a 36-amino acid peptide shuttle, as well as a series of analogues that retain some of the properties of the parent peptide.

This has eliminated the need for venom to be extracted directly from scorpions.

They have studied the efficiency of these compounds in cell models of the BBB and have demonstrated that the peptide called MiniCTX3 has the capacity to transport compounds of different nature across the BBB “with great efficiency”.

Animal venoms for the brain

In the same way that traditional medicine uses natural products such as plants and flowers to treat a range of diseases, the IRB Barcelona lab has sought inspiration from venoms with the objective of identifying peptide shuttles.

“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, research associate and co-leader of the research.

“There are only two or three groups worldwide devoted to shuttle peptides. We are working on a number of strategies, and one of them is venoms,” says Giralt.

In previous studies, the research group made some chemical modifications to a peptide from bee venom, namely apamin, and also obtained a shuttle with BBB permeability.

After these positive results, the lab wanted to address whether venoms could provide a universal source of peptide shuttles.

“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.

This study is another example of ground-breaking research finding inspiration in nature and has produced another shuttle that can enhance drug transport into the brain, potentially transforming treatment for diseases such as Alzheimer’s and Parkinson’s diseases.

Photo courtesy of Ester Inbar, available from http://commons.wikimedia.org/wiki/User:ST

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