Sarah Greising is an associate professor and associate director for research and external funding in the University of Minnesota's School of Kinesiology, part of the College of Education and Human Development. She and her research team investigate volumetric muscle loss (VML), where a person has had some loss of the volume of their muscle, such as through injury or through surgery, that results in a chronic functional deficit that can't be recovered.
Addressing Muscle Loss with Regenerative Rehabilitation
Greising’s work is centered around regenerative rehabilitation, a rapidly growing field that brings together new technologies that regenerate tissues with rehabilitation science “to increase the functional gains made by patients following injury or disease, and ultimately improve their quality of life,” according to the American Physical Therapy Association. The Department of Defense (DoD) has been interested in this work because of the large number of soldiers, particularly in the recent military engagements, who have had battlefield injuries that have resulted in severe muscle loss.
“I was always interested, and still am, as to how muscle recovers or maybe why it doesn't,” said Greising, who received her PhD in Rehabilitation Science from the University of Minnesota Medical School in 2011.
After postdoctoral work at the Mayo Clinic, Greising was a research physiologist at the U.S. Army Institute of Surgical Research (USAISR) in San Antonio, Texas, one of the three military treatment facilities in the U.S. where injured soldiers receive care.
“That's where my work really focusing on injured service members started; it definitely gave me more context,” Greising said. “It puts a face with the problem, essentially. There is a rehab facility, the Center for the Intrepid, where patients are living there, and you see them every day. It’s a really integrated research and clinical center.”
The soldiers at USAISR who had suffered VML were often faced with a question about whether to keep or have amputated severely injured limbs. Through her work, Greising hopes that she can provide a better choice for those who choose what the medical profession calls limb salvage, providing hope for potential restoration of some muscle function in severely injured limbs.
At USAISR, she and her former University of Minnesota PhD classmate Jarrod Call, by then an assistant professor at the University of Georgia, began collaborating on a project to evaluate whether early rehabilitation interventions could improve a soldier’s muscle’s functional recovery when compared to late-stage and unstructured rehabilitation, which has been the more standard approach for care. They developed new animal models that could mimic injury, inactivity, and physical rehabilitation, and measure muscle function and metabolism, that is, its ability to convert nutrients into energy to power muscle function.
In 2018, Greising was recruited back to the University as an assistant professor of kinesiology, and she brought a portion of her DoD-supported research portfolio with her.
“Minnesota has a great skeletal muscle community that is vast across lots of different colleges,” Greising said. “And I just essentially kept building one of the major focuses of the work—understanding why the muscle after injury is not responding to things that we think it should.”
A Promising New Approach
With the support of the DoD Greising and Call began testing a series of small molecule drugs already approved by the FDA for other purposes to find ones that could improve the muscle mass and the metabolism, the effects of which could be layered on to physical rehabilitation. They homed in on one promising drug called formoterol, a component of asthma inhalers, that had showed signs of increasing muscle growth in studies for treatment of cancer cachexia and spinal cord injuries, and they investigated whether combining the drug with a modified equivalent of physical rehabilitation could recover muscle mass and function.
“In the human cases that we are modeling in animals, rehab alone isn't really doing much of anything,” Greising said. “This drug has done a few things that we have not seen happen in previous VML models before, in that it started to improve muscle mass and metabolism, and, more importantly, the function of the muscle. So we are hoping that the drug can kickstart the recovery of muscle function when added to rehab, and we have seen some great success in our animal models.”
Greising and Call, who each employ 10-12 people in their respective labs, are progressing to large animal studies to validate the success they’ve already seen in their rodent models, and they are laying the groundwork for a potential next step, which would be clinical trials in humans.
“This was a smaller award that grew into a bigger award, and then now we are moving it into large animals to see if we can get it into the clinic,” she said. “This has been a series of awards now that has pushed us down this pathway with really a lot of continued support from the DoD, which has kept support for injured soldiers as a high priority.”
Dual Use Technology for Broader Application
Although the potential VML treatment is being developed at the behest of DoD, the clinical trials would likely be open to trauma victims beyond the military, and, if successful, the treatment would be widely available and accessible to patients across the country. If that happens, it would be an example of dual use technologies, ones that have been developed by the military but have broad civilian applications, be that farm or motor vehicle accidents.
“I personally like working with the DoD because it's sort of a known quantity to me now,” she said. “I’ve gained a really good understanding of how the DoD focuses their efforts and how you can focus your research to support their questions--kind of in parallel. DoD is very focused on a product. They want the answer to this question, and they don't necessarily need all the science on how to get there. At the same time, our lab also has NIH funding, for more basic or mechanistic science of how this treatment works, all the stuff that the DoD maybe doesn't as much want to fund, but it all works really well together. Ultimately, I think it helps my colleagues and me scientifically.”