Strand Life Sciences, a technology innovation major, has developed a computer simulated virtual liver to predict and explain mechanisms of drug-induced hepatotoxicity. The virtual liver, which was created using a mathematical model of a normal liver physiology of a rat, can now be used to assess the toxicity of drug molecules. The virtual liver requires some input parameters related to metabolic rates that are measured for each drug molecule using assays on rat liver cells.
“The company has now completed its stage one validation studies on 8 drug molecules to measure the toxicity and mechanisms. The 14 assays for these molecules were contracted to a CRO in California. Under the contractual obligations, Strand has fully retained all IP in the developed assays. Strand will now enlarge the study by another 25 molecules with the assays now run in India as a second stage of validation. Several global pharma companies have already been engaged in talks with our chief scientific officer Dr Kas Subramanian, and are willing to send their compounds for tests,” Dr Vijay Chandru, chairman and CEO, Strand Life Sciences and president, Association of Biotechnology Led Enterprises (ABLE) told Pharmabiz.
The in-vitro/in-silico platform can be used by scientists at Strand to profile in-vivo toxicity of small molecules in rats and plans are to extend it to other mammals eventually. To bring the platform to this first stage of validation has been a major task involving over 6 years of intense R&D and has the potential of being a game-changing breakthrough in improving the odds of taking unsafe molecules out of contention early in drug discovery. This development also has the potential to impact the wasteful use of some animal studies. “Our approach could result in the reduction of the number, time, and expenditure associated with animal experiments. It will allow companies to have a clearer comprehension of how the drug leads and candidates affect the liver in the pre-clinical phase,” he added.
This development is significant since Europe has adopted REACH, a European Community Regulation on chemicals and their safe use (EC 1907/2006) enforced from June 1, 2007, which could impact safety studies of all chemical products from 2013, as some restrictions will be placed on the use of animal tests.
Stage II of the research initiative is being funded under the BIPP of the Department of Biotechnology where Strand sent in a proposal seeking a Rs.10 crore grant/soft loan of which Rs.2.5 crore has been sanctioned for the first phase of the study. The plans are to incubate this project with the help of CCAMP at the National Centre for Biological Sciences (NCBS), Bangalore. Strand is simultaneously in the process of building a dedicated lab facility located within the campus of the University of Agricultural Sciences, Bangalore that will be commissioned in early 2012. Strand is also in talks with investors to raise a series B of approximately Rs.45 crore ($10 million) to fund various growth plans including the commercialization of the virtual liver asset.
“Although a gold standard for drug induced toxicity is still elusive, the promise is that as in-silico models become accurate from pre-clinical and clinical end points , we should be able to get more information using virtual models to predict and gain insights into the mechanisms of various types of toxicities,” said Dr Chandru.