An EU-funded project shows how researchers can unlock the medical benefits of venom more quickly, promising breakthrough treatments for health problems such as heart disease, cancer and diabetes.
The venom of poisonous animals contains toxic proteins that attack the nervous system, the heart and blood cells and blood circulation to kill prey. However, in small quantities the same proteins can relieve disease symptoms in humans and save lives.
According to the EU-funded VENOMICS project, there are 170,000 known venoms, with several hundred toxic proteins, or toxins, in each. All have very different structures and ways of acting on the body and are considered a huge source of potential drugs.
Despite this, there are only a handful of venom-based drugs on the market, says Rebeca Minambres, in charge of dissemination at Spain-based Sistemas Genómicos, a project partner. She explains this is because traditional methods of identifying useful toxins are slow, expensive and need large amounts of venom.
Now VENOMICS has developed a quicker, more efficient system for finding beneficial toxins. The technique is up to five times faster and needs about 20 times less venom than conventional methods. It opens the door to cheaper drug development in the search for treatments for life-threatening diseases, says Minambres.
The VENOMICS approach could do more than reduce the cost of drugs, she adds. It will allow industry to explore even the smallest venomous animals and help researchers screen biological material for other useful properties connected to a wide variety of health problems.
More leads in less time
Standard venom analysis involves breaking toxins down into smaller and smaller protein sequences. Researchers analyse how each sequence behaves until they find the part that acts on the body – the active molecule.
This is a slow and expensive process, taking from one to two years, says Minambres. It also limits the range of venoms that researchers can use. This is because large quantities of venom are needed, ruling out using small or rare animals, which represent 90 per cent of venomous animals.
Using VENOMICS’ approach, identifying possible drug ingredients takes only half a year and uses natural toxin more efficiently. Taking a small amount of venom, it maps – or sequences – its genetic code and protein structures.
With this information, researchers identify the venom’s small toxin molecules – or peptides – that have interesting properties. They then reproduce these peptides using bacteria, or chemical synthesis to create a bank of peptides organised so researchers can study them in large numbers very quickly using high-throughput screening.
Innovative processes
Venom for developing the new method came from 120 poisonous animals, which created two challenges.
Many of the animal venoms had not been studied before, while several species, such as ants, wasps and sea snails, are too tiny to produce much venom. So the project team devised new protocols for sequencing the unstudied venoms, along with methods for reducing the amount of venom needed.
The team is now refining the procedure for making toxin copies, with the first batch in the pipeline. Quality control tests will follow, then tests to analyse the medical properties of the selected peptides.
The final goal of this project is to produce a bank of 10,000 venom peptides. The consortium estimates that there could be several potential new drugs for different medical areas and plans to investigate medical uses of these toxin molecules in 2015, says Minambres.
Researchers outside the project could also benefit from the new testing method. Minambres adds: “The proteins and toxins we identify will remain secret to be developed into potential drugs, but the methodology and research on how animals make proteins will be made public when the project ends.”
Project details
- Project acronym: VENOMICS
- Participants: France (Coordinator), Spain, Portugal, Denmark, Belgium
- Project reference: 278346
- Total cost: € 9 360 275,25
- EU contribution: € 5 998 786,65
- Duration: November 2011 - October 2015