Zebrafish used to catch heart data
toxicity screening service using zebrafish as a model for assessing
drug effects on cardiac function.
The technique measures QT prolongation - a potential drug-induced effect on the heart that can cause cardiac problems and even death. In recent years, several drugs have been withdrawn from the market because adverse events related to prolongation of the QT interval. The US-based CRO, Phylonix Pharmaceuticals, said the zebrafish (Danio rerio) is "extremely cost-effective compared to larger animal models, and its embryo is already established as a powerful model for studying genetics and developmental biology". Zebrafish is now a widely-used organism for genetic and developmental studies and articles validating it as a model for researching drug-induced QT prolongation have recently appeared in Circulation and AJP Heart and Circulatory Physiology, due to the comparable nature of zebrafish and human heart electrophysiological properties and electrocardiogram (ECG) patterns, including the PR interval, QRS complex and QT interval. Phylonix records ECG signals from the fish using a data acquisition system belonging to ADInstruments, called PowerLab, and uses another of this company's software programmes, Chart Pro ECG Analysis Module, to analyse this data and generate QT prolongation information on an investigational compound. "Phylonix has been offering this screening service now for 6 months. There is no other CRO that offers this particular screen at the moment," ADInstruments spokesperson Matt Dilworth told DrugResearcher.com. According to Patricia McGrath, Phylonix president and CEO, "We decided to get into this area because we could see that the pharmaceutical industry was being mandated to do QT prolongation testing for all their drugs, so if we could get the model to catch on, we hoped we'd catch some customers!" Indeed, Herman Scholtz, corporate vice president and worldwide head of Clinical Pharmacology - early phase development, told Outsourcing-Pharma.com in an earlier interview that the firm is witnessing a trend towards the increase in QTc studies in Phase I. "QTc studies are a growing market because they need to be done as a precautionary measure on all drugs that may have the ability to affect the heart," said Scholtz. This was mandated by the FDA two years ago following a number of concerns over drugs that were found to induce rhythmic disturbances. Meanwhile, UK preclinical services provider Summit, formerly known as Vastox, is using a chemical genomics approach for high throughput, small molecule in vivo screening in whole organism models, one of them based on zebrafish, to generate toxicity and teratogenicity data. The firm recently secured three pilot screening deals - each valued at $100,000 - with Merck, Johnson & Johnson's Belgium outfit, and Servier to conduct blind screening of known compounds in order to evaluate the effectiveness of such technology. "We are hoping to convince these firms that zebrafish could be a useful adjuvant to their preclinical screening and as a result, increase the size and breadth of the deals we now have in place," Darren Millington, Summit CFO told Outsourcing-Pharma.com in an earlier interview. Millington said the company has worked with six of the top ten pharma companies on zebrafish pilot programmes in some capacity in the past year, with "most of them" leading to follow-on work of some kind. According to the firm, in many cases this approach generates data which is highly predictive of toxicity in mammals at a much earlier stage in discovery than with standard animal models such as rodents, rabbits and dogs, and as a result elicits cost savings. "For example, in glaucoma, we have a fish model that gives us results in days or weeks, compared to the weeks and months that it takes with rabbit models, the current standard," said Millington.
