Harnessing the therapeutic power of venom
fully exploit the known therapeutic effects of venoms.
French venom company, Latoxan, and a Swiss biopharma company, Atheris Laboratories have joined together to create a venom fraction library called Kitoxan, to speed up and simplify research. The library is sold in 96-well plates for drug screening, with each well containing between five and ten peptides "to facilitate the identification of the active peptide once a hit is found", according to the company. As the Latoxan CEO, Harold de Pomyers, explained to DrugResearcher.com, venoms from plants and animals are a sophisticated mix of hundreds of peptides. All of these interact with the body and some could potentially be used as drugs to treat a huge variety of diseases. Drugs extracted or evolved from natural sources are nothing new to pharma companies. However, in the past it has been difficult for researchers to work with venoms - in the mix of molecules how could they know which one is exerting the positive effect? The new library should make that question much easier to answer, opening the door to hundreds of potential new drugs, said the companies. Pomyers explained that Latoxan has a snake farm on site with over a hundred species to milk for their venom. The company also travel to countries where other venomous animals live, such as scorpions, amphibians and spiders. The scientists collect and milk them before returning them unscathed to their natural habitat. Once the venoms from around 200 different species have been collected, the first step in creating the library is to remove poisonous proteins from the mix. Choosing from 20 venoms initially, gel permeation is used to filter out molecules over a certain weight. Pomyers said: "This was done because most screening uses live cells and these proteins would kill them." Then, Latoxan use a technique called HPLC to separate the venom mixes into another 20 parts, giving 400 freeze-dried fractions in all. Of those 400, 80 fractions (from four different venoms) are selected for a given project and placed on 96-well plates ready for use in drug screening. If this initial venture with Atheris proves successful, Pomyers said that Latoxan will try and build a more expansive joint venture with the biopharma. Despite the difficulties associated with working with venoms, their therapeutic potential is undisputable - there are many drugs both marketed and in development extracted or derived from toxins. The idea of using snake venom to treat heart disease may seem strange, yet that is exactly what Bristol-Myers Squibb did when they used the venom of a pit viper, Bothrops jararaca, to develop Capoten (captopril). Other drugs tied to venoms include Schering-Ploughs Integrilin (eptifibatide), to treat acute coronary syndrome. That drug is a platelet glycoprotein IIb/IIIa recptor inhibitor. However, it is not just heart disease exploiting venom. Other drugs from these sources are approved to treat cancer, stroke, Type II diabetes, pain relief and Alzheimer's, for example. Elan Pharmaceuticals has also tasted success with venoms. It developed Prialt (ziconotide), a non-opioid pain killer that blocks N-type calcium channels. The drug is a synthetic version of a peptide found in cone snails (also called sea snails). Latoxan plan to develop the tool to use the other venoms already at their disposal and also collect new types of venom from other animals, including those from cone snails. The Kitoxan project could run for some time: "[There are] 100,000 venomous species in the world and millions of potential hits for drug discovery." On top of those already mentioned, other big pharma companies, such as Eli Lilly and Abbott, are also reaping the rewards of venoms and research in this field is sure to continue for some time yet.
