Mapping Our Molecules
The quest for precision exercise medicineWendy Meyer | CCTSI Jun 25, 2019
Every day on the University of Colorado Anschutz Medical campus, hundreds of research studies and clinical trials take place. Each one is important in its own way. However, this summer Professor Wendy Kohrt will be launching an exercise study the likes of which no one has ever seen. It is so big (involving more than 2,300 individuals across the nation) and will result in information so voluminous (tens of thousands of bio-specimens that will result in millions of data-points for future research), you might think of it as the summer blockbuster of biomedical research.
The study is called MoTrPAC (pronounced “motorpack”) and it stands for Molecular Transducers of Physical Activity Consortium. Funded by the National Institutes of Health (NIH), this six-year program is the largest targeted investment into the mechanisms of how physical activity improves health and prevents disease.
Dr. Kohrt explains, “We have a lot of knowledge that exercise is good for many aspects of health. It makes your heart and lungs healthy, your muscles and bones strong. It prevents obesity. It prevents many different health conditions and disease processes.
“Yet we know very little about how exercise does that—the molecular or cellular mechanisms that make exercise beneficial.”
Through MoTrPAC, researchers aim to develop a so-called molecular map of tissue-specific and circulating signals produced by physical activity. This knowledge should allow researchers and doctors to develop individually targeted exercise recommendations for specific diseases and conditions, and better help those who are uncertain whether exercise may be as therapeutic as a medication.
“If we know, for example, that exercise turns on the same signal that a drug for diabetes turns on, we can prove exercise is a good therapeutic alternative for this process that is affected by drugs,” said Dr. Kohrt. “This will stimulate the next wave of research to understand how exercise can be used as medicine.”
The impact for CU Anschutz
A study this large naturally involves many players. CU Anschutz is just one of six clinical sites across the country that will be enrolling volunteers for the study. Dr. Kohrt is the principal investigator of CU’s portion of the grant, and she will be directing all of the activity in Colorado.
Her MoTrPAC team consists of four full-time and three part-time professional research assistants, a site coordinator, an exercise supervisor, a bio-specimens manager, three physicians, two nurse practitioners, a biostatistician, a data manger and five investigators. Pictured below (left to right) are some of the team members: Claire Newman, MS, Daniel Bessesen, MD, Andrew Hepler, Ellie Gibbons, Kathleen Gavin, PhD, Catherine Jankowski, PhD, Bryan Bergman, PhD and Terry Witten MS-MPH, RD.
The study is complex not just because it involves a large number of volunteers but because of the many steps involved each time a study participant comes to the clinic for a research visit.
Because MoTrPAC explores what happens to our bodies on the molecular level before, during and after we exercise, blood and tissue samples must be taken before and after exercise. This means that a volunteer would come in and first rest; then a specially trained research nurse would take blood samples along with muscle and fat biopsies. Then the volunteer would engage in either aerobic exercise or weight lifting. The nurse would again take blood and tissue samples after the exercise. (Some participants may be randomized into a group that does no exercise at all.)
When asked what it’s been like getting ready to start working with hundreds of study volunteers, professional research assistant Claire Newman, MS said, “Hectic! “It will be a full team effort.” Each time a volunteer comes in for a visit, he or she will likely interact with a team of at least six people.
During its operation, MoTrPAC will rely heavily on the resources of the Colorado Clinical and Translational Sciences Institute (CCTSI) and its core laboratories, outpatient clinical and translational research clinic (CTRC) and a state-of-the-art exercise research facility on the third floor of the Leprino Building. When the new Anschutz Health Sciences building is complete in 2021, both the CCTSI and MoTrPAC will move onto the sixth floor of the facility.
“We developed our comprehensive set of research resources for initiatives exactly like this one,” said CCTSI Director Ronald Sokol, MD. “We are looking forward to supporting MoTrPAC in whatever way we can.”
“Our set up is ideal,” said Dr. Kohrt (pictured at right). “When we had our site visit from the NIH, they were so impressed that we have a one-stop shop for everything related to this protocol, all on the same floor.”
The impact for researchers everywhere
One of the things that distinguishes MoTrPAC from most other NIH funded research is that it is an exploratory study.
MoTrPAC Site Coordinator Ellie Gibbons explains, “In other words, we have not identified specific aims or goals. We do not have a hypothesis. We are gathering information in order to create a molecular map of tissue-specific and circulating signals produced by physical activity. We don’t know what is going to happen, and that is what makes this different and exciting!”
In addition to the fact that it is an exploratory study, MoTrPAC is unusual in terms of the breadth of science involved. In addition to the six clinical trial sites, (of which CU Anschutz is one) MoTrPAC will include:
seven chemical analysis sites
three preclinical animal study sites (they will conduct physical activity studies in animal models)
a bioinformatics center to disseminate data and tools to the entire research community, and
a coordination center to harmonize activities across the consortium.
All of the information gathered will be stored in a publicly accessible database that scientists can use to study almost every organ and tissue in the human body. Ultimately, the research findings resulting from this program could help scientists and clinicians define optimal physical activity recommendations for people at various stages of life, as well as to develop precisely targeted regimens for individuals with particular health needs.
According to Dr. Francis Collins, director of the NIH, “Anybody who has got a good idea, about what is going to be a pretty large dataset, can start to sort it through and see what we can learn about those molecules, how they work and what we can do to improve what we advise people about exercise.”
In this way, MoTrPAC will be a resource today and dozens of years into the future for researchers everywhere.
The impact for volunteers
However, none of this pathbreaking science will be possible without the involvement of thousands of volunteers across the nation.
“A study of this magnitude has never been done, which means we need a lot of research participants to help us answer our important questions,” said Renee J. Rogers, PhD, one of the investigators in the national MoTrPAC consortium.
Dr. Kohrt is hoping that Colorado, with its healthy citizens and lovers of the outdoors, will be the perfect place to find willing volunteers. Researchers are looking for all ages of individuals who are healthy. They are also seeking participants who are sedentary but who have the capacity to exercise; and they will look for volunteers who routinely exercise.
Volunteers who are part of the MoTrPAC study will receive a 12-week exercise program and access to state-of-the art gym facilities. They will also receive information about their fitness level and their body composition. In addition, all volunteers will be compensated for their time.
“This is our first step into precision exercise medicine,” said Dr. Kohrt. “We are looking for people who want be on the leading edge of the wave to develop this incredible knowledge base.”
If you are interested in learning more about how to volunteer for the study, go to the MoTrPAC website or call 720-848-6408.