Researchers at IRB Barcelona modify chlorotoxin—a small protein present in scorpion venom with blood-brain barrier permeability—to transport drugs into the brain.
The barrier, which protects the brain, prevents drugs used for the treatment of neurological diseases and brain tumours from entering the organ.
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).
The barrier serves to protect the brain from toxic substances, but it also prevents many potential drugs for the treatment of neurological diseases and tumours from entering this organ. “About 98% of drugs that could have therapeutic applications cannot be used because they cannot cross this barrier,” explains the head of the lab, Ernest Giralt.
The researchers have chemically synthesised chlorotoxin and a series of analogues that retain some of the properties ofas the parent peptide. 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”.
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, 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, these scientists inspired in a peptide from bee venom, namely apamin, had made some chemical modifications and 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 it has produced another shuttle that can enhance drug transport into the brain.
The research was funded by the Ministry of Science, through ERDFs, and the Catalan Government.
Reference article:
Cristina Díaz-Perlas, Monica Varese, Salvador Guardiola, Jesús García, Macarena Sánchez-Navarro, Ernest Giralt and Meritxell Teixidó
From venoms to BBB-shuttles. MiniCTX3: a molecular vector derived from scorpion venom
Chemical Communications (2018) DOI: 10.1039/C8CC06725B
In its “Preguntas Big Van” section, the newspaper La Vanguardia has interviewed IRB Barcelona researcher Meritxell Teixidó about her project, which seeks to develop “shuttles” that transport drugs into the brain. In this regard, 98% of drugs that start to be developed to treat diseases of the central nervous system are abandoned because they cannot cross the barrier that protects the brain. Inspired on bee and scorpion venom, Teixidó has identified several families of peptides capable of crossing this barrier.
Meritxell Teixidó, a researcher at IRB Barcelona, has been interviewed on the TVE2’s documentary ¡Qué animal! about her work with peptides from scorpion and bee venom in search of drugs that can reach the brain. "These poisons are able to reach the brain, which explains their toxicity. It is precisely this capacity that attracts us to examine their applications," explains Teixidó.
Link to TVE
It is estimated that one in four people will require brain treatment at some point. While there are drug candidates for most diseases of the brain, the blood-brain barrier (BBB) poses an impassable obstacle for most of these compounds and a bottleneck for the delivery of drugs that could cure these patients.
