Venom To Cure Disease, On The Frontier Of Modern Snake Medicine
A European program has been researching how the pharmaceutical industry could use the peptides found in venomous creatures for new therapeutic medicines.
PARIS — Nicolas Gilles points to a dozen metal boxes in a refrigerator, all filled with preserved samples of animal toxins, mini proteins that are among the most dangerous substances found in Mother Nature — secretions made to paralyze, suffocate or kill. The refrigerator contains more than 4,000 from 201 venomous species: snakes, spiders and cone snails, among them.
This researcher at the Atomic Energy and Alternative Energies Commission outside Paris coordinates a European project called Venomics, which has been studying therapeutic uses of animal venom. Launched four years ago, the project ended a few weeks ago with a closing conference designed for the media at the French National Museum of Natural History in Paris. It was an opportunity for participants from all over Europe to make assessments about their activities and talk about leads for the future.
The idea of creating drugs made from animal substances that are designed to attack prey or protect against an enemy isn't new. "To produce their neurotoxic, cardiotoxic or hemotoxic effects, venoms affect specific cells of living organisms through peptides," Gilles explains. Some of these mini proteins are capable of fixing themselves to the sensory neurons and ion channels of cells, to change their functions or block their production.
And that's precisely how the pharmaceutical industry could use these proteins: to produce new, more precise treatments with fewer side effects and to treat pains or illnesses such as diabetes, cancer or cardiovascular diseases.
Of course, because of the high production costs, the complexity of the manufacturing processes and the immune problems that they pose, peptide drugs are still rare on the market. In 2010, there were barely 60, and only five of them came from animals. But Gilles says that using biotechnologies "could change the situation." Especially when it seems worthwhile. Extracted from the saliva of a Mexican lizard called the Gila monster, Byetta is prescribed to treat type 2 diabetes and is among the pharmaceutical industry's best sellers, with sales of more than $1 billion.
The objective of Venomics was to advance the research on these animal toxins, and to sequence the peptides contained in the venoms of 201 different types of animals, then produce them individually. The aim was to build a library of samples that a pharmaceutical manufacturer could test.
But first the researchers had to obtain the raw material for their studies: venoms and venom glands from a wide variety of animals, some of them exotic and not exactly docile. "Two expeditions in French Guiana, another in Mayotte and a final one in French Polynesia were dedicated to the gathering of insects, myriapoda, cone snails and terebridae mollusks," says Gilles' colleague Frédéric Ducancel, who personally dove in the Polynesian Makemo atoll, a lagoon surrounded by coral reefs, to collect samples. "The rest — snakes, scorpions, spiders, lizards, bees, centipedes, ants, sea anemones, stonefish and rays — were supplied by amateur breeders, and by Alphabiotoxine, a specialized company based in Belgium."
The team then began analyzing the material using highly complex techniques. From this 25,000-peptide bank, 4,000 were then synthesized through chemical methods, or even, says Renaud Vincentelli from the University of Aix-Marseille, "by using refolded expression processes that consisted of producing them through bacteria."
Finally, even though this wasn't the primary objective of Venomics, biologists managed to establish that about 30 of these mini-proteins resembled cellular sensors and could likely interest the pharmaceutical industry.
"We could imagine setting up a new European project dedicated to the scientific exploit of this data in order to understand, for instance, why individuals within the same species of cone snails present different venoms according to their level of development or the region they're in," Gilles explains. "It could also aim to enlarge the toxin bank in order to make it attractive to the pharmaceutical industry market."