Apofore Founder Publishes Studies Identifying Apolipoprotein A-IV as New Potential Target for Type 2 Diabetes Therapeutics

PNAS report suggests Apolipoprotein A-IV plays important role in regulating glucose homeostasis

CAMBRIDGE, Mass.--(BUSINESS WIRE)--May 22, 2012 - Apofore Corporation today announced that its scientific founder at the University of Cincinnati, Patrick Tso, PhD, Professor in the Department of Pathology and Laboratory Medicine, has published new data demonstrating that the naturally occurring protein, Apolipoprotein A-IV (apoA-IV), reduces blood sugar and increases insulin secretion in mouse models of diabetes. The research published in the current online early edition of the Proceedings of the National Academy of Sciences (PNAS), suggests apoA-IV is a promising new target for developing treatments for Type 2 diabetes. Apofore, which has licensed the technology from the university, is building on this work to develop novel Type 2 diabetes therapeutics, beginning with a recombinant form of apoA-IV.

ApoA-IV is secreted from the small intestine in response to lipid absorption. The protein has previously been shown to play a potential role in the regulation of food intake, lipid metabolism and mediation of the inflammatory process. Studies have also shown that apoA-IV is significantly increased in humans following gastric bypass, and this was coincident with the amelioration of diabetes.

“Our studies have identified a novel function of apoA-IV as a potent regulator of insulin secretion and glucose homeostasis,” stated Dr. Tso, who is also the company's scientific founder. “Along with Apofore, the next phase of research will further characterize apoA-IV's role in diabetes and lay the groundwork for clinical studies to evaluate its potential benefits in patients.”

“Although great strides have been made with Type 2 diabetes treatments in recent years, there is still a substantial need for new therapeutic approaches that normalize glucose and reduce cardiovascular inflammation,” noted Christopher K. Mirabelli, PhD, President of Apofore and a Managing Director at HealthCare Ventures. “Dr. Tso and his team have succeeded in identifying a very interesting and novel target for diabetes therapeutic development. Apofore was established to advance this promising research, beginning with a recombinant form of apoA-IV, into clinical trials to determine its potential role in the diabetes treatment paradigm.” HealthCare Ventures is funding Apofore.

Dr. Tso and his team studied mice that were deficient in apoA-IV (known as apoA-IV-/- knockout mice) and found that these knockout mice had reduced insulin secretion and impaired glucose tolerance. These same knockout mice, when fed a diet high in fat developed impaired glucose tolerance to a greater degree than wild type mice on the same diet. However, knockout mice on the same high fat diet that received apoA-IV injections showed improved insulin response to glucose.

Additionally, the Tso group evaluated whether the beneficial effects of apoA-IV administration could be extended to other models of diabetes. The team evaluated a diabetic mouse model known as KKAy, characterized by obesity, insulin resistance and hyperglycemia. In this model, injection of apoA-IV resulted in a significant decrease in glucose levels and a corresponding increase in insulin secretion during the period when glucose levels decreased most rapidly.

The paper is entitled, Apolipoprotein A-IV improves glucose homeostasis by enhancing insulin secretion. The study's co-authors include Sean Davidson, PhD, Tammy Kindel, Alison Kohan, Silvana Obici, PhD, Fei Wang and Stephen Woods, PhD, all from the University of Cincinnati; and Kathryn Corbin and Craig Nunemaker of the University of Virginia, Charlottesville.

About Type 2 Diabetes Mellitus

Type 2 diabetes is a lifelong (chronic) disease in which there are high levels of sugar (glucose) in the blood. Type 2 diabetes is the most common form of diabetes. In Type 2 diabetes, either the body does not produce enough insulin or the cells do not respond adequately to insulin. Insulin is necessary for the body to be able to use glucose for energy. When you eat food, the body breaks down all of the sugars and starches into glucose, which is the basic fuel for the cells in the body. Insulin takes the sugar from the blood into the cells. When glucose builds up in the blood instead of going into cells, it can lead to diabetes complications, such as cardiovascular disease, stroke, blindness (retinopathy), nerve damage (neuropathy), and kidney damage (nephropathy). The US Centers for Disease Control and Prevention estimates that there are approximately 26 million Americans who have Type 2 diabetes, 8.3% of the US population.

About Apofore Corporation

Apofore Corporation is a focused company founded by Patrick Tso, PhD and funded by HealthCare Ventures. ApoA-IV, the first therapeutic being prepared for clinical trials, has promising pre-clinical data supporting potential use in patients with Type 2 diabetes mellitus. For more information, please visit www.apofore.com.

About HealthCare Ventures

HealthCare Ventures is a leading life science venture capital firm investing in preclinical and early clinical stage “Focused Companies” with the potential to transform patient care. Since its founding in 1985, HealthCare Ventures has raised $1.6 billion across nine funds and has invested in 105 companies, 67 as startup ventures. For more information, please visit www.hcven.com.

 

Contact: Apofore Corporation
Jeff Packman, 617-714-0359
jpackman@hcven.com

 

Posted: May 2012

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