Drug testing with synthetic livers

Scientists from clinical intelligence company Empiriko have developed chemosynthetic liver technology which could enable the testing of drug candidates without using animals. The research was presented at the 247th National Meeting & Exposition of the American Chemical Society (ACS).

Dr Mukund Chorghade, chief scientific officer of Empiriko and president of THINQ Pharma, said the development of new pharmaceuticals still depends heavily on animal testing, even after the European Union enacted regulations in 2010 to reduce the practice. Even ignoring the issue of animal rights, Dr Chorghade said it is “a very painstaking, laborious and costly process. Frequently, scientists have to sacrifice many animals and, even after all that, the results are not optimal”.

When researchers discover a new compound that could address a human health need, they firstly test it on animals to see if it’s toxic. After giving an animal a test drug, the experimental compound does its designated job in the body until it is broken down in the liver by a group of enzymes known as cytochrome P450. The researchers then try to detect the resulting molecular by-products, or metabolites, which are often responsible for causing side effects.

Empiriko’s chemosynthetic livers (Biomimiks) are catalysts that act similarly to cytochrome P450, meaning researchers could figure out the metabolic profiles of drugs by mixing them with Biomimiks in test tubes. Dr Chorghade said, “These chemosynthetic livers not only produce the same metabolites as live animals in a fraction of the time, but they also provide a more comprehensive metabolic profile, in far larger quantities for further testing and analysis.”

Other possible applications could include the use of Biomimiks to detoxify blood for liver transplant patients; or to predict side effects when multiple drugs are taken together. When Dr Chorghade and his collaborators looked at two drugs commonly taken together - one for high cholesterol and the other for type 2 diabetes - they found that the cholesterol drug sped up the breakdown of the diabetes drug, which could potentially lower its effectiveness.

Dr Chorghade’s group has tested more than 50 drugs so far to show that the catalysts accurately mimic how the human body processes them. He said that they are working to get that number up to 100, which is what the US Food and Drug Administration requires for regulatory approval.