CARMEL, Indiana – A novel pharmacological treatment demonstrated significant weight loss in animal models of obesity according to a scientific paper to be published in the October issue of Nature Chemical Biology. The paper, co-authored by researchers Richard DiMarchi, Ph.D. (Indiana University), Matthias Tschöp, M.D. (University of Cincinnati) and colleagues, chronicles work with novel peptides under development at Marcadia Biotech that have generated a significant weight loss effect and reduction of fat mass in rodent models of obesity after once-weekly administration. An online version of the paper was released on July 13.

The scientific paper describes a new approach combining the mechanisms of two natural hormones to accentuate weight loss within one drug candidate. Glucagon and GLP-1 are two peptide hormones that are known predominantly for their regulation of glucose metabolism. The Nature publication describes the chemical and biological integration of their pharmacology to deliver enhanced weight loss and glucose control without any apparent side-effects.

“While potential commercial products that may come from this research are still early in the development phase, it does advance the prospect that pharmacological treatment of obesity with single agents may be possible,” said Fritz French, CEO of Marcadia Biotech. Current pharmacological treatment of obesity has limited effectiveness and safety issues have been a continuing concern, “these new drug candidates offer considerable potential and we are committed to advancing them into clinical testing,” French said.

The newly published research, some of which has been recently presented by the authors to scientific peers at various conferences, also showed positive effects on lipids metabolism (normalization of plasma lipids and reduced fatty liver disease).

DiMarchi, who serves as Marcadia’s Chief Scientific Officer, is a professor of chemistry and holds the Linda and Jack Gill Chair in Biomolecular Studies at Indiana University, Bloomington and is a former group vice president of the Lilly Research Laboratories. DiMarchi also was a co-founder of Marcadia and serves on the company’s board of directors. The molecules that are at the core of the research were discovered by DiMarchi and colleagues at IU’s department of chemistry in Bloomington and are licensed to Marcadia.

Tschöp, an MD and neuroendocrinologist, who is an associate professor of Endocrinology and Medicine at the University of Cincinnati's Obesity Research Centre and Genome Research Institute, conducted the research for Marcadia Biotech. The pre-clinical testing and in vivo biology validation of the new Marcadia compounds was led by Tschöp and performed in his obesity research laboratory at the University of Cincinnati School of Medicine. Tschöp also serves on Marcadia Biotech’s Scientific Advisory Board.

Titled “A novel glucagon and GLP-1 co-agonist eliminates obesity in rodents,” the peer-reviewed published manuscript is available online at www.nature.com/nchembio.

About Marcadia Biotech
Marcadia Biotech is a biopharmaceutical company focused on developing therapeutic products that will greatly improve the daily life of people with diabetes and obesity. Marcadia has a robust pipeline of peptide drug candidates for treatment of type 2 diabetes and obesity with superior profiles to those of currently marketed blockbuster drugs. The company is also developing a glucagon analog for acute treatment of severe hypoglycemia. It was founded in 2006 and is located in Carmel, Indiana.

About Obesity and Diabetes
Obesity, a medically defined chronic disorder, and diabetes related to obesity represent two of the biggest health risk factors of the 21st century, as documented by the World Health Organization. Experts list clinical obesity, a condition that often directly contributes to the onset of diabetes, as the second leading cause of preventable U.S. deaths. Chronic obesity is linked by medical research to higher risk of type 2 diabetes, high blood pressure, several types of cancer and other severe medical conditions. Direct and indirect U.S. costs related to obesity (and its diabetes-related complications) are estimated to exceed $100 billion annually. (According to the Center for Disease Control and Prevention, obesity is defined as a body mass index (BMI) of 30 or greater. BMI is calculated from a person’s weight and height and provides a reasonable indicator of body fatness and weight categories that may lead to health problems.)

Official release from Nature Chemical Biology

A hormone hybrid cuts out fat

DOI: 10.1038/nchembio.209

A bifunctional hormone analogue that controls glucose processing can reduce body weight, as reported online this week in Nature Chemical Biology. This study could impact how obesity and diabetes are controlled.

Glucagon and glucagon-like peptide-1 (GLP-1) are natural hormones that regulate glucose metabolism. Though these two hormones are similar in structure, they differ in their amino acid sequence and biological function. Previous studies report that glucagon and GLP-1 can suppress appetite or cause weight loss by increasing the body’s calorie usage, but the full spectrum of their potential as therapeutics has been unknown.

Richard DiMarchi and colleagues combined the sequences of these two known hormones to create new hormone analogues that activate the receptors for both glucagon and GLP-1. The researchers found that a single injection of the best synthetic analogue in mice decreased their body weight by 25% and fat mass by 42% after one week, with greater effect from repeated treatment.

Though further research would be needed before these hormone analogues could be utilized as a drug in humans, the results point to a new approach for the treatment of obesity and adult-onset diabetes.

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