SAN DIEGO, June 12 /PRNewswire/ -- Entelos, Inc., the leader in
biosimulation technologies for pharmaceutical research and development,
announced today that it presented data in two poster sessions at the 65th
Annual American Diabetes Association Meeting. One presentation described
the results of a comprehensive analysis on the time-dependent effects of
treatment on therapeutic outcomes in the non-obese diabetic (NOD) mouse, the
most common animal model of human type 1 diabetes (poster #1280). The second
presentation describes the Type 1 Diabetes PhysioLab(R) platform, a large-
scale mathematical model of diabetes pathogenesis and intervention in the NOD
mouse (poster #1279).
"Despite the success of numerous therapies in the NOD mouse, translational
efforts to prevent or treat the human disease have been disappointing," said
Mikhail Gishizky, Chief Scientific Officer of Entelos. "We developed this
model in collaboration with the American Diabetes Association to advance our
understanding of type 1 diabetes pathogenesis using predictive mathematical
models, and improve the rationale for advancing potential therapies into human
clinical trials."
Time-Dependent Effects on Treatment Outcomes
NOD mouse studies were examined for the dependence of treatment efficacy
on protocol parameters. A comprehensive review of all intervention studies
published through mid-2004 was conducted, including the tabulation of
treatment outcomes, onset and duration times, dose, and study length. In one
analysis, 395 agents or agent combinations (n = 696 treatment protocols) were
examined. Quantitative analysis revealed that contrary to a common perception,
there were no significant differences (P > 0.05) in the probability of
protection whether treatments were started early (< 4 weeks) or late (greater
than or equal to 4 weeks). Similar results were obtained when comparing
treatments initiated before vs. after 6, 8 or 10 weeks of age. A second
analysis, all agents tested in prediabetic or diabetic NOD mice were examined
(n = 760 treatment protocols). Examination of these data for single agent
efficacy revealed that, for some agents, efficacy correlated with timing of
treatment initiation and treatment duration. Agents were classified into three
groups for which 1) earlier administration was better, 2) later administration
was better, and 3) prolonged treatment was required for efficacy. These
findings suggest that while at a global level, both early and late treatments
can be effective in the NOD mouse, certain agents require specific treatment
windows for disease modulation.
The Virtual NOD Mouse
Applying a systems modeling approach to aid type 1 diabetes research, a
novel mathematical model was developed, the Type 1 Diabetes PhysioLab
platform. The primary purpose of this platform is to improve understanding of
disease pathogenesis in the NOD mouse model, and then use that understanding
to help translate results of interventions in the NOD mouse to expected human
clinical outcomes. The platform focuses on islet Beta cell autoimmunity and
tolerance and related mechanisms and interventions. The virtual diabetic mouse
exhibits characteristic insulitis in the islets and develops diabetes after
twelve weeks of age if untreated. A number of interventions that were
developed using the NOD mouse are also represented in the PhysioLab platform.
Research using this platform will help define the mechanisms driving
pathogenesis in the NOD mouse and how differences between mouse and human
biology may lead to differences in therapeutic response.
About Type 1 Diabetes
Estimates are that as many as one million or more Americans have type 1
diabetes, an immunemediated disease that leads to destruction of the insulin-
producing beta cells in the pancreas and the need for daily insulin injections
throughout life. Type 1 diabetes usually arises in children or young adults.
Scientific understanding of this disease in humans has been limited by the
difficulty of identifying those people likely to develop the disease as well
as practical considerations in studying humans with the condition. At this
time there are no preventative treatments available for type 1 diabetes.
About Entelos
Entelos, Inc. (http://www.entelos.com) is a biopharmaceutical company
focused on discovering and developing new therapies for metabolic and
inflammatory disorders. Our mission is to leverage our unique predictive
capability in human biology to dramatically improve how medicines are
discovered, developed, and brought to market. Using our proprietary PhysioLab
biosimulation platforms - -- computer-based mathematical
models of human
disease, we systematically uncover the biological mechanisms underlying a
disease in order to identify potential points of therapeutic intervention and
the patients most likely to benefit. In addition to our internal research
programs, Entelos partners with pharmaceutical and biotechnology organizations
worldwide.
Entelos and PhysioLab are registered trademarks and/or service marks of
Entelos, Inc. All other trademarks are the property of their registered
owners.
Contacts:
Entelos, Inc.
Barry Sudbeck
sudbeck@entelos.com
Tel: +1.650.572.5479
McKinney Chicago
Alan Zachary
azachary@mckinneychicago.com
+1.708.707.6834
SOURCE Entelos, Inc.
 back to top
Related links:
http://www.entelos.com
CONTACT:
Barry Sudbeck of Entelos, Inc.,
sudbeck@entelos.com, +1-650-572-5479; Alan Zachary of McKinney
Chicago, azachary@mckinneychicago.com, +1-708-707-6834, for
Entelos, Inc.
|
