The fat cell syndicate

FOSTER CITY, Calif.—A cross-disciplinary diabetes research consortium led by Pfizer Inc. that will examine insulin signaling in fat cells to increase understanding of diabetes and obesity will be enhanced by in silico research, the pharma announced last month.

Entelos Inc., a biotechnology company specializing in predictive computer models of human and animal disease physiology, will lend its PhysioLab model of whole-body metabolism to the Insulin Resistance Pathways (IRP) Project, an academic-industry research collaboration funded by Pfizer.

Under its agreement with Pfizer, Entelos will work with the pharma to apply computational approaches to identify new drug targets relevant to diabetes and obesity alongside researchers from the University of California, Santa Barbara (UCSB); the California Institute of Technology; the Massachusetts Institute of Technology; and the University of Massachusetts.

Pfizer's initial funding for the IRP project is $14.4 million over the next three years, with an option to extend the project for an additional two years.

In the first phase of the IRP Project, the consortium's academic research partners will collect experimental data about insulin pathways within adipose human cells. After analyzing the data supplied by the other computational groups and then developing mathematical models of the insulin signaling pathways, the researchers will then apply those models to identify targets for therapeutic action.

Entelos' role will be to assess the potential efficacy of treating those targets, using the company's whole-body model of Type 2 diabetes. Entelos' technology also will serve as a key integration tool to bring all the primary data into context for the wide variety of patients seen in the clinic, says Dr. Mike Reed, a lead scientist from Entelos working on the IRP Project.

"Entelos' ultimate goal is to help discover new medicines for the treatment of Type 2 diabetes and alleviate human suffering," Reed says. "We believe that integrating Entelos' predictive simulation capabilities into pharmaceutical drug discovery is the most effective approach to accelerate this process. Entelos' participation in the IRP will clearly demonstrate the value of this approach."

"My view for Entelos is for them to bring the proverbial holistic context to the project," says Dr. Frank Doyle, professor of chemical engineering and associate director of the Institute for Collaborative Biotechnologies at UCSB. "While our project is very carefully focused on the behavior of the adipose cells, the ultimate pharmaceutical objective or targets have to account for the context of the whole body. The only folks I am aware of in the academia or business worlds who are that far along in making whole-body simulations of disease is Entelos."

If the first phase of the project proves successful, a second, two-year phase will extend these studies to other insulin-sensitive tissues such as liver, muscle and possibly hypothalamic or beta cells. According to Dr. Preston Hensley, senior director in Pfizer's Worldwide Exploratory Science & Technology organization, Pfizer has four main objectives to accomplish.

"We want to get a deeper knowledge about the biology of these cells and link up with some genome-wide association studies," he says. "We want to come out of this with a prioritized list of effective targets. We want to gain a better understanding of cell-based safety issues. Lastly, we're also hoping some diagnostic tools will come out of this."

In a major departure from traditional industry-academia practice, the collaboration agreement allows the partners to publish and patent any discoveries—including enhancements expected to be made to Entelos' PhysioLab—made in the course of their research. Data may be presented publicly following approval by Pfizer. DDN