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MARS Initiative

An update from the MARS initiative...

Patients have benefitted by an increased knowledge of how effective a procedure will be for them
The MARS initiative has been responsible for some of the most seminal work published on the mechanisms of action, microbiota and metabolic signalling

In 2007, Ethicon began the Metabolic Applied Research Strategy (MARS) initiative, a multi-year, multi-million dollar commitment to support fundamental research into obesity and other metabolic disorders. Now in its sixth year, Bariatric News talks to Dr Elliott Fegelman, Medical Director at Ethicon, about the benefits the MARS programme is bringing to surgeons and patients around the world…

Dr Elliott Fegelman

“The MARS initiative was started because while we could see excellent results bariatric and metabolic surgeons were obtaining but as a community, we couldn’t really explain why,” began Fegelman. “As a result, Ethicon established a partnership with surgeons to give them the opportunities to provide some answers and to look for less invasive methods of achieving the same results.”

As part of the initiative, the company started to support the work of two research laboratories: the Metabolic Diseases Institute (MDI) at the University of Cincinnati, and the Obesity, Metabolic & Nutrition Institute (OMNI) at the Massachusetts General Hospital (MGH). These two institutions had the capbility to perform basic and translational research, and were committed to understanding the physiological changes that can occur after bariatric and metabolic surgery.  

“In a broader sense, what MARS has really allowed us to understand is that the gastro-intestinal tract is a hugely complex sensory organ with complex signalling mechanisms.”

In essence, these two centres were charged with helping to deconstruct, understand and reinvent bariatric procedures in ways that improved outcomes, focusing on fundamental research around obesity and metabolic disorders.

Research

Dr Lee Kaplann

The research undertaken at MGH is led by Dr. Lee Kaplan, Associate Professor of Medicine at Harvard Medical School, Director of the Obesity, Metabolism, and Nutrition Institute, and Director of the Weight Center at MGH. Dr. Kaplan's extensive research is focused on the physiological and molecular mechanisms of gastrointestinal regulation of energy balance and metabolic function. His group has pioneered the development and use of rodent models for weight loss surgery and gastrointestinal devices to explore these mechanisms.

Dr. Randy Seeley, Professor of Medicine at the University of Cincinnati College of Medicine, Director of the Cincinnati Diabetes and Obesity Center, and Director of the Obesity Research Center, is leading the work on the actions of various peripheral hormones in the central nervous system that serve to regulate food intake, body weight and the levels of circulating fuels.

These two centres have performed the majority of the efforts concentrating on the basic science level, which includes understanding surgical procedures’ mechanisms of action at the tissue, cellular, molecular and genetic levels.

Dr Randy Seeley

Understanding

“The MARS initiative has been responsible for some of the most seminal work published on the mechanisms of action, microbiota and metabolic signalling, and this work continues to be built upon,” said Fegelman. “In a broader sense, what MARS has really allowed us to understand is that the gastro-intestinal tract is a hugely complex sensory organ with complex signalling mechanisms.”

“When we think about the GI tract in those terms, the techniques and procedures become less important and the effects on the sensory organ become paramount, and this is the focus of many current investigations,” he continued. “It has been known for years that the gut and the brain communicated, what has changed recently is that we have begun to understand what those signalling mechanisms look like, what parts of the brain respond to these signals and how the GI tract adapts.”

Such has been the rate of discovery that the MARS initiative has achieved to date: it’s been responsible for more than 65 publications, including 14 peer-reviewed articles, which have been published across the whole spectrum of the medical field, underlining the multifaceted aspects of metabolic disease.

Patient benefits

Not only has the MARS initiative brought new insights into our understanding of how bariatric and metabolic surgical procedures work, but it has made a significant difference in the real world - to patients.

“Patients have benefitted by an increased knowledge of how effective a procedure will be for them. For example, we can now inform patients about how a bypass will benefit them more than a band,” Fegelman explained. “We can discuss the rationale of the procedure and explain how GLP-1, insulin sensitivity etc., will impact the outcome of surgery.

“From personal experience, I explain to patients how a procedure changes their physiology; I can see that patients are much more confident in the procedure. Bariatric surgeons are no longer just performing surgical procedures; through dedicated research, such as the MARS Initiative, they are now in a position to inform as well as operate.”

Multi-disciplinary

Ethicon is not only working with bariatric and metabolic surgeons to discover new and valuable insights into metabolic disease, the company is also supporting other specialties. As part of the MARS initiative, in 2010, the company donated U.S. $500,000 in funding to support up to three, three-year research grants through the American Diabetes Association.

The research grants support the investigation of the specific mechanistic effects of bariatric surgery on diabetes. They also support translational research to improve the clinical understanding of various bariatric procedures as potential treatment options for people with obesity and Type 2 diabetes mellitus.

This is a further example of how metabolic disease is not limited to just one medical specialty or field and therefore requires a multi-disciplinary approach to discover new ways to combat the disease.

“The MARS Scientific Advisory Board (SAB) changes every year as they try to bring new people on board and identify new ways of looking at the data and patient experience. The constantly evolving Advisory Board is based on the questions we are asking or being asked and the expertise we are looking for,” said Fegelman. “It is primarily surgeons at this point, mostly because this is the group that we have the most experience of working with and because they have the greatest experience of bariatric and metabolic surgery.”

“However, as we move forward I am sure that the SAB will continue to evolve and will include diabetologists and endocrinologists, nutritionists and bariatric physicians, as the gulf in dialogue between the surgical and medical viewpoints regarding this patient population narrows.”

"...the MARS initiative has provided incremental changes in our knowledge and understanding, and that any future developments will come about by an evolutionary rather than revolutionary process"

The future

“I don’t think we are too far away from providing a solid economic argument for bariatric and metabolic surgery. If we can identify the optimum time to treat a patient so the disease-costs are significantly reduced by surgical intervention, that is an investment I believe society will pay.”

“I believe the ‘holy grail’ would be to find some insulin-like treatment that we could give to the patient subcutaneously that would mimic hormonal signalling or a drug that functions as the serotonin uptake inhibitors do to treat depression; that affects the signalling mechanism at the hypothalamus. As a result, surgery would only be considered in the most critical or an emergent case, similar to how cardiac surgery is performed today.

“Let’s not forget, this is a super complex system with multiple inputs and  responses, and the body has evolved highly-developed defences against manipulation. So whether we get there in a decade or longer I really couldn’t say,” Fegelman concluded. “What I can say is that working with Drs. Kaplan and Seeley on the MARS initiative has provided incremental changes in our knowledge and understanding, and that any future developments will come about by an evolutionary rather than revolutionary process.”

Additional information

For more information regarding the MARS Initiative, please click here

To educate others on the critical findings of the principal researchers of the MARS initiative, Ethicon has hosted 11 MARS Outreach Courses since late 2011.  Due to the overwhelming interest in the information, 12 additional global courses are planned for early 2014. Contact your local Ethicon representative if you are interested in attending a MARS Outreach Course.

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