Mark Billadeau Posted March 21, 2008 Report Share Posted March 21, 2008 A new class of anthelmintics effective against drug-resistant nematodes Nature 452, 176-180 (13 March 2008) Ronald Kaminsky1, Pierre Ducray2, Martin Jung1, Ralph Clover3, Lucien Rufener1,4, Jacques Bouvier1, Sandra Schorderet Weber1, Andre Wenger1, Susanne Wieland-Berghausen2, Thomas Goebel2, Noelle Gauvry2, François Pautrat2, Thomas Skripsky2, Olivier Froelich1, Clarisse Komoin-Oka5, Bethany Westlund3, Ann Sluder3 & Pascal Mäser4 Novartis Centre de Recherche Santé Animale, CH-1566 St Aubin (FR), Switzerland Novartis Animal Health Inc., CH-4002 Basel, Switzerland Cambria Biosciences, Woburn, Massachusetts 01801, USA Institute of Cell Biology, University of Bern, CH-3012 Bern, Switzerland Laboratoire Central Vétérinaire de Bingerville, BP 206, Lanada, Côte d'Ivoire Correspondence to: Ronald Kaminsky1 Correspondence and requests for materials should be addressed to R.K. (Email: ronald.kaminsky@novartis.com). Abstract Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics—the benzimidazoles, imidazothiazoles and macrocyclic lactones—has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics. The compounds paralyze the worms by targeting previously uncharacterized receptor subunits involved in the worms' neurotransmissions. Knowing the mechanism of action at the outset may help monitor, if not delay, eventual drug resistance should the compounds reach the veterinary market… parasitologists Roger K. Prichard & Timothy G. Geary of McGill University Source: Chemical & Engineering News March 17, 2008 Mark Quote Link to comment Share on other sites More sharing options...
juliepoudrier Posted March 21, 2008 Report Share Posted March 21, 2008 Wow, good news for those of us who are now using cydectin with nowhere to go! J. Quote Link to comment Share on other sites More sharing options...
Mark Billadeau Posted March 21, 2008 Author Report Share Posted March 21, 2008 That's why I posted it when I read about it in C&E News. I don't know how long it will be before (or if) it is brought to the veterinary market. I did see patents from Novartis covering these compounds. Mark Quote Link to comment Share on other sites More sharing options...
Bill Fosher Posted March 21, 2008 Report Share Posted March 21, 2008 Probably a good idea to continue to operate as if this wormer will never come to pass. From what I understand, it will take at least five to 10 years for a drug to get from the stage this one is at to operational utility in the field. And then there's the question of whether they'll label it for sheep. But, it's a good first step and one that we should celebrate. It's the first new class of livestock dewormer in what, 40 years? Quote Link to comment Share on other sites More sharing options...
Mark Billadeau Posted March 21, 2008 Author Report Share Posted March 21, 2008 Bill is right on the time frame from discovery to market; but the first step has been made. THE OVERALL R&D process and time frame for animal pharmaceuticals are similar to those of their human counterparts, including discovery of an active pharmaceutical ingredient, formulation, clinical testing, and government approval for marketing. Companies say the average development journey for a veterinary product is five to nine years. Source: Big Pharma Chases Dogs And Cats Chemical & Engineering News Mark Quote Link to comment Share on other sites More sharing options...
Deacon Dog Posted March 21, 2008 Report Share Posted March 21, 2008 ...time frame for animal pharmaceuticals are similar to those of their human counterparts... Anyone familiar with the process know why that is? Seems to me clinical tests could be run for meat and short-term effects on live animals and allow the product to go to market labeled to indicate testing is ongoing, and any long-term effects are unknown. Quote Link to comment Share on other sites More sharing options...
Rebecca, Irena Farm Posted March 21, 2008 Report Share Posted March 21, 2008 We'd need to know not just the effects on the livestock, Tony, but on other animals (humans included) that would be exposed to the new product once it's in the food chain, or in the environment. It would really stink to rush a product through and then discover that the feces of treated animals kills beneficial worms in the soil, fresh water fish, and songbirds and waterfowl. I'm glad there's something in the pipeline but as Bill said I'll proceed with my parasite management practices like there's no hope on the horizon. Quote Link to comment Share on other sites More sharing options...
Caroline Reichard Posted March 21, 2008 Report Share Posted March 21, 2008 Wow, good news for those of us who are now using cydectin with nowhere to go! J. Julie, I lost a dozen sheep to Barbour pole worms a few years back, and at that time it seemed that Cydectin was my only option; it did save the life of the rest of my flock that year. Since then, I have had very good luck w/ levamisole, which is a small fraction of the price. Perhaps the old lemonade-mix would work for you, too. CR Quote Link to comment Share on other sites More sharing options...
Mark Billadeau Posted March 24, 2008 Author Report Share Posted March 24, 2008 We're probably closer to release of the drug than we think. World Patent Application: WO/2005/121075 AMINOACETONITRILE DERIVATIVES AND THEIR USE FOR CONTROLLING PARASITES ON WARM-BLOODED ANIMALS Filed: 2005 Mark Quote Link to comment Share on other sites More sharing options...
Mark Billadeau Posted March 24, 2008 Author Report Share Posted March 24, 2008 Tony, This pdf is from the FDA. OVERVIEW OVERVIEW of the of the ANIMAL DRUG APPROVAL PROCESS These are the key studies listed and the data for these must be collect under strict guidlines and testing conditions and the data is then reviewed by the FDA. Public Safety: toxicology, residue chemistry, etc. Target Animal Safety Environmental Safety Effectiveness Manufacturing Chemistry Mark Quote Link to comment Share on other sites More sharing options...
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