Virtual diabetes research

ALEXANDRIA, Va.—The American Diabetes Association (ADA) and Entelos Inc., a biotechnology company specializing in predictive biosimulation, are opening their doors to allow the research public to test-drive their in silico diabetes research center capabilities and Entelos' virtual mice testing platform.

For nearly three years, ADA and Entelos have collaborated on the development of a Type 1 Diabetes PhysioLab platform, a large-scale, computer-based mathematical model of the non-obese diabetic (NOD) mouse, which is the simulation engine behind Realab for type 1 diabetes. The technology has been available for use by researchers at pharmaceutical companies, but the ADA and Foster City, Calif.-based Entelos recently announced they will give ADA members free access to it, enabling them to investigate the onset, progression and treatment of diabetes. Non-member researchers will also be able to access the platform for a fee.

"We decided that because type 1 diabetes is still a complex issue, we should broaden access to the technology being used by pharmaceutical companies in a proprietary manner to the research public," says Scott Campbell, VP of research at the ADA. "We're trying to get researchers interested in it and thinking outside of the box. The open access to the pared-down model allows them to try the technology and determine if it will benefit them. If they find it valuable, they can generate an agreement to work with Entelos on the full version."

Entelos' PhysioLab captures the physiology of pancreatic cell autoimmunity and tolerance from birth until disease onset. Virtual NOD mice are constructed using equations that mathematically represent cellular functions and biochemical interactions in tissues critical for the pathogenesis of type 1 diabetes. Functions at the biochemical and cellular levels are integrated and quantitatively linked via mathematical equations, making simulation and prediction of biological outcomes possible.

The Realab Web-based tool facilitates the design and submission of experiments and clinical protocols. Once a Realab protocol is submitted, simulation results are available in Realab within 24 hours for later analysis at the user's convenience. Researchers can visualize the predicted outcome of the Realab protocol using graphs and other tools to investigate the underlying biological mechanisms responsible for each predicted outcome.
Entelos CEO and President James Karis says the increased access to Realab may enhance researchers' capabilities to rapidly test virtual mice and patients using fewer animals, run more decisive clinical trials, and save time and money.

"One of the greatest disappointments for the pharmaceutical industry is having experimental compounds that show early promise in animals that later fail miserably when tested in humans," Karis says. "Scientific teams at Entelos discovered subtle but important differences between species that can have a big impact on interpreting results of animal studies and on designing clinical trials. Our models and predictive platforms help to better translate results and design experiments to make animal studies more meaningful and relevant for finding effective medicines for patients."

Although in silico research has not yet seen widespread adoption, Campbell sees the increased access to Realab as an opportunity to show researchers that the traditional research paradigm can be changed. He adds that ADA and Entelos are hoping to further their collaboration by building an in silico biosimulation of a NOD mouse and morphing it into a predictive human model.

"The time is right for people to buy into this concept," he says. "Opening access to this technology may help people see that you can indeed build a model of a biochemical or metabolical system that allows you to conduct virtual experiments. The technology won't replace clinical trials or animal research, but it can be used as a tool to supplement it."