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Artificial Liver For Drug Tests

Posted by: admin in Pharmacy Drugs on July 01st, 2009

If you have hay fever, headaches or a cold, it’s only a short way to the nearest chemist. The drugs, on the other hand, can take eight to ten years to develop. Until now animal experiments have been an essential step, yet they continue to raise ethical issues. “Our artificial organ systems are aimed at offering an alternative to animal experiments,” says Professor Heike Mertsching of the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB in Stuttgart. “Particularly as humans and animals have different metabolisms. 30 per cent of all side effects come to light in clinical trials.” The test system, which Professor Mertsching has developed jointly with Dr. Johanna Schanz, should in future give pharmaceutical companies greater security and shorten the path to new drugs. Both researchers received the “Human-centered Technology” prize for their work.

“The special feature, in our liver model for example, is a functioning system of blood vessels,” says Dr. Schanz. “This creates a natural environment for cells.” Traditional models do not have this, and the cells become inactive. “We don’t build artificial blood vessels for this, but use existing ones - from a piece of pig’s intestine.” All of the pig cells are removed, but the blood vessels are preserved. Human cells are then seeded onto this structure - hepatocytes, which, as in the body, are responsible for transforming and breaking down drugs, and endothelial cells, which act as a barrier between blood and tissue cells. In order to simulate blood and circulation, the researchers put the model into a computer-controlled bioreactor with flexible tube pump, developed by the IGB. This enables the nutrient solution to be fed in and carried away in the same way as in veins and arteries in humans. “The cells were active for up to three weeks,” says Dr. Schanz. “This time was sufficient to analyze and evaluate the functions. A longer period of activity is possible, however.” The researchers established that the cells work in a similar way to those in the body. They detoxify, break down drugs and build up proteins. These are important pre-conditions for drug tests or transplants, as the effect of a substance can change when transformed or broken down - many drugs are only metabolized into their therapeutic active form in the liver, while others can develop poisonous substances. The researchers have demonstrated the basic possibilities for use of the tissue models - liver, skin, intestine and windpipe. At the moment, the test system is being examined. Within two years it could provide a safer alternative to animal experiments.

Source:
Heike Mertsching
Fraunhofer-Gesellschaft

MedImmune continues to advance its commitment to pediatric research with today’s announcement of the first observational prospective study designed to assess the burden of respiratory syncytial virus (RSV) among preterm infants 32-to-35 weeks gestational age (GA) in outpatient settings during their first year of life.

The study also seeks to gather virology data regarding the national onset of the RSV season across the four geographic regions established by the U.S.

Biolex Therapeutics, Inc. announced that it has completed patient enrollment in the SELECT-2 Phase 2b trial of its lead product candidate Locteron® for the treatment of chronic hepatitis C. Locteron, controlled-release interferon alpha 2b, is designed to improve patient care by providing a more convenient once-every-two week dosing schedule and by reducing the side effects, including flu-like symptoms, associated with pegylated interferons, the current standard of care.

The Phase 2b trial is being conducted in the United States and Europe in over 100 treatment-naïve, genotype-1, chronic hepatitis C patients. Patients were randomized into one of four dosing cohorts, the 320, 480 or 640 µg dose of Locteron (administered once every two weeks) or a control arm consisting of PEG-Intron® (1.5 µg/kg, administered every week), with all patients receiving weight-based ribavirin. Patients will be treated for 48 weeks and will be followed for an additional 24 weeks to determine the sustained virologic response (SVR) rate. The interim results after 12 weeks of treatment are expected to be used as the basis for the selection of the Locteron dose(s) for Phase 3 trials.

“We are pleased with the response to the SELECT-2 Phase 2b trial and the fact that we were able to rapidly complete enrollment using substantially less clinical sites than we originally anticipated,” said Mr. Jan Turek, Biolex’s President and Chief Executive Officer. “Locteron is the only controlled-release interferon alpha under development and research to date suggests that this attribute may reduce side effects and has the potential to improve patient compliance and to reduce discontinuation rates. Extensive market research recently completed confirms that there is a substantial commercial opportunity for Locteron if a tolerability advantage is demonstrated in more advanced clinical testing. We look forward to receiving key results from SELECT-2 during the fourth quarter of this year.”

Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.

Locteron Overview

Locteron is a controlled-release interferon alpha designed to improve patient care in the treatment of hepatitis C through a more favorable side-effect profile and dosing convenience compared to existing pegylated interferon products. In contrast to Locteron’s controlled-release mechanism, the currently approved products, Pegasys® and PEG-Intron, and the investigational product Albuferon®, are immediate-release products that lack a controlled-release mechanism. Interferon alpha serves as the foundation of current combination therapy for hepatitis C patients, and all major hepatitis C drug candidates currently in clinical trials are being studied in combination with interferon alpha. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.

Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron’s controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons and Albuferon. This controlled-release mechanism is designed to reduce the frequency, duration and severity of side effects, including flu-like symptoms, commonly experienced by patients treated with pegylated interferons and with Albuferon.

Source
Biolex Therapeutics

View drug information on Pegasys.

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