Entelos builds in silico model for diabetes

The platform, built by the biotech company Entelos, will permit the translation of data and results generated from animal models into likely human responses under similar conditions (i.e. specific drug therapies).

The prospect of translating observations with in silico​ models bodes well for the future of drug development and research, assuring a more accurate translation of what is observed in preclinical models to human response, says the company.

Dr Mikhail Gishizky, chief scientific officer for Entelos​ said: "Translating observations made in preclinical animal model systems to human in vivo responses is a complex issue posing significant challenges to the development of therapeutics for treating human disease."​

"In the case of the NOD mouse, therapies that looked promising in animal models have not demonstrated efficacy in treating patients with type 1 diabetes. The drug developer needs to know, 'if the mouse gets better, will the patient?"​

The model will be built in collobaration with the American Diabetes Association (ADA) and a Scientific Advisory Board to guide and oversee the development of the NOD PhysioLab platform.

Animal models are currently seen as the best alternative to the practical considerations in studying humans who suffer from the same condition. However, the limitations of species differences often result in discrepancies between animal and human therapeutic responses.

In silico​ animal models have the advantage of quickly and quantitatively linking observed animal behaviours with predicted human response.

"The NOD PhysioLab platform will empower researchers to study the mouse model in silico and help them bridge the gap between animals and patients with type 1 diabetes,"​ said Gishizky.

The dramatic rise in the number of potential but poorly validated targets and preliminary hit compounds has led to several model systems to be constructed, each with its own advantages, and is intended to bridge the gap between in silico​ and animal models.

Xenogen has developed in vivo​ biotrophic imaging technologies that enable real-time analysis of drug effects on biological processes in living animals.

This allows researchers to collect data for effects on internal organs without the need of surgery, and for the time-course effects from the same animals. However, image resolution using this method is relatively low, limiting its application.

Where animal models have been used, researchers have developed model systems using vertebrates (zebrafish) and invertebrates (the fruit fly, Drosophila melanogaster​ and the nematode Caenorhabditis elegans​). The small size, high fecundity and experimental tractability of these animals enable cost-effective and rapid screening of compounds.

Several biotechnology companies have developed Drosophila​ based drug discovery technology platforms. Exelixis has a gene-knockout array generated from a large collection of stocks that each contain a single transposition insertion in the fly genome.

The zebrafish is the only vertebrate species for which large scale forward genetic screens have been carried out and in many mutants obtained from these genetic screens display phenotypes that mimic human disorders, including cardiovascular disease, neurodegeneration, cancer and blood disease.

These mutants not only identify genes that may be involved in diseases but also can be used for drug screening.

Researchers at Phylonix Pharmaceuticals have tested a number of compounds that showed anti-angiogenic effects in mammals including SU5416 and flavopiridol. They found that a drug's effect on vessel inhibition in zebrafish correlated well with the effects of angiogenesis inhibitors in humans.

Because angiogenesis is involved in other diseases, such as diabetic retinopathy and macular degeneration, the angiogenesis assays are also useful for discovering therapies for these diseases.