Skeletal muscles control our movements, posture, and strength. Cardiac muscles pump our hearts. Smooth muscles contract the uterus during childbirth, move nutrients through our digestive systems, and control the flow of blood in our vascular system—but they are poorly understood. “It’s wide open,” says Kathleen Morgan of the field she’s devoted her career to. “We know almost nothing about these muscles.”
Morgan, a professor of health sciences, believes that smooth muscles hold the clues needed to connect two of the world’s deadliest diseases—cardiovascular and Alzheimer’s—and to develop cures. Cardiovascular disease, including strokes and heart disease, kills more people than any other cause—nearly 18 million annually, according to the World Health Organization (WHO)—and no cure exists. Cardiovascular disease can lead to damage of the blood vessels in the brain and the loss of cognitive ability, known as vascular dementia. Cures for diseases of the brain, such as Alzheimer’s, have also proven elusive. What if, Morgan wonders, the brain damage that leads to dementia is originating in the vascular system? There’s already an established correlation: as many as 80 percent of people with Alzheimer’s also have cardiovascular disease, according to the Alzheimer’s Association.
Our hearts push blood to our brains via the aorta, the central highway of the body’s circulatory system. The aorta’s smooth muscles prevent the blood from speeding into the brain so fast that it ruptures blood vessels—which can happen suddenly, as during a stroke, or more gradually, as the aorta stiffens with age and loses its buffering power. The seemingly complex phenomenon of dementia, which includes challenges with reasoning and memory loss, could be traced back to the basic contractions of a blood vessel. “It’s a motor thing—it’s muscles contracting at the wrong time or in the wrong way,” Morgan says.
One common target of Alzheimer’s research is amyloid plaque, a protein that can build up in the brain and kill neurons. Morgan wonders if plaque is the product of a greater problem: vascular bleeding. “When blood vessels get stiff, and you’re pounding with high blood pressure on the brain, maybe that is the initial cause,” she says. “That’s my hypothesis—that vascular dementia comes first.”
To explore her hypothesis, and to find ways to prevent vascular bleeding, Morgan had to learn more about the brain. She started by talking with her Sargent colleagues, including Helen Barbas, a professor of health sciences and director of the Neural Systems Lab. “She’s considered one of the most important people in the field of smooth muscle physiology,” Barbas says of Morgan. “It’s not an easy transition [to studying the brain] because you’re navigating something that’s much more complex than the muscle.”
Next, Morgan wants to learn how the different forms of the protein control contraction and relaxation in smooth muscles. A calponin-based therapy, properly targeted, could potentially control the smooth muscles in our blood vessels. But how to steer that therapy to its intended target? Morgan has been collaborating with BU’s College of Engineering on a technique to deliver drugs to hyper-specific parts of the body—such as the blood vessels around the heart—by guiding microbubbles of inert gas with an ultrasound beam. A drug coupled with an effective delivery system could have an immense impact. According to the WHO, 55 million people live with dementia today and 10 million more are diagnosed each year.
Morgan’s father was one of those people. At the time she was deciding to focus her research on smooth muscles and vascular dementia, he was dying from Alzheimer’s disease. “I watched him go from a bright man who taught me an awful lot to a guy who didn’t know who I was,” she says. “That really motivated me.”
After years of study, Morgan is confident in the progress she’s made. “I’m absolutely convinced that we can find an approach for Alzheimer’s if we can address the vascular problem,” she says.