Deadly venom from snakes, frogs, scorpions and insects could lead to novel treatments for cardiovascular disease, cancer, and diabetes, thanks to a new toxin library, which can be screened to find leads for new drugs.
While there are already a handful of drugs derived from venom, new research is enabling scientists to more easily analyse how toxins work and reproduce them in a lab.
When a venomous animal bites or stings, the cocktail of toxins that constitute a venom act rapidly in the body. They’ve evolved to be highly specific to particular molecules, binding to them tightly, like a key into a lock. And because of stable cross-links in their structure, toxins aren’t easily broken down by the body.
It is this ability to seek out and bind to specific molecules that makes scientists believe they might be useful in targeting disease.
‘Animal toxins are known to display fabulous pharmacological properties, with high affinity and selectivity,’ said Dr Nicolas Gilles, who coordinates the EU-funded VENOMICS project. ‘And that’s why they represent a very interesting source of drug candidates.’
In order to create a library, or biobank, of different toxins and their properties, VENOMICS researchers have developed new techniques to study the composition and properties of thousands of toxin molecules that make up venom.
They are building on the success of the 2007-2011 CONCO project, also funded by the EU, which identified the active compounds in the venom of a single species of cone snail to create a ‘synthetic library’ of potential drug candidates.
Now, the researchers hope to analyse a whole range of venom samples, most of which have not previously been investigated by science, in order to produce a biobank of brand new drug leads.
‘Animal toxins are known to display fabulous pharmacological properties.’
Dr Nicolas Gilles, CEA, France
‘Previously, it’s been a very slow and costly task to identify the active toxins in a venom, which can be composed of 1 000 different compounds,’ explained Dr Gilles. ‘This is one reason why the pharmaceutical companies so far have hesitated to invest in this field. But now, things are changing.’
The techniques developed by VENOMICS to analyse toxins are faster and more efficient than traditional methods, which require larger volumes of venom and involve gradually breaking it down until the active molecule is isolated – a process than can take up to two years.
In contrast, VENOMICS researchers can scan for useful toxins in a matter of months. Their methods also require 20 times less venom, meaning that the miniscule volumes produced by tiny animals – such as ants and ticks – can finally be studied.
Dr Gilles said: ‘90 % of venomous animals are less than one centimetre in size. Classical technologies are simply not adapted to that scale, making impossible the use of this phenomenal biodiversity.’
173 000 venomous animals
There are 173 000 venomous animals, representing a collection of 40 million molecules of interest. VENOMICS has succeeded in analysing 200 animal species, the largest number of venomous animals ever studied.
A team at the University of Liège, Belgium, was responsible for obtaining the genetic sequences of molecules for analysis, and a Spanish company called Sistemas Genómicos was able to uncover how genes were expressed in venom glands, thanks to the development of original code and new sequencing software.
These two complementary techniques allowed the generation of the biggest databank to date, consisting of 25 000 genetic sequences. From these sequences, 5 000 toxins are now under production by Aix-Marseille University and the CEA Saclay laboratory in France.
The last phase of the project will see scientists conduct screening of the toxin library against specific disease molecules to establish leads for cardiovascular disease, cancer, pain and diabetes drugs.
‘The future of VENOMICS will be the transferring of this technology to private companies,’ said Dr Gilles, ‘transforming our pilot into a larger-scale, industrial project.’
The VENOMICS team aren’t shooting in the dark: a dozen or so major drugs derived from venoms have already made it to market. Here are a few examples:
Captopril: Based on teprotide, sourced from the Brazilian arrowhead viper, this blood vessel relaxing agent is commonly used to treat hypertension.
Tirofiban: First approved in 1998, this anticoagulant was designed to mimic a short sequence found in the venom of the African saw-scaled viper. It’s given to patients recovering from heart attacks, or suffering with angina.
Ziconotide: Chemically identical to a peptide found in cone snail venom, this painkiller (brand name Prialt) can be injected into spinal fluid to stop pain signals reaching the brain.
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