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Scaling a Tall Peak

Blog1In June, the world mourned the loss of American boxing great Muhammad Ali, who long suffered the effects of Parkinson’s disease (PD). While too late for Ali, the Penn community of clinicians and researchers are hard at work finding new ways to detect the disease so that the next generation of moms, dads, husbands, wives and children with PD can benefit from early detection -- and maybe even get a PD test along with blood pressure screening at their annual physical.

Matt Stern, MD, the Parker Family Professor of Neurology and director of Penn’s nationally renowned Parkinson’s Disease and Movement Disorders Center, and his colleagues started on a quest nearly a decade ago for a way to diagnose the disease earlier. “Our hope is for there to someday be a test to show a risk for PD much like taking one’s blood pressure does for cardiovascular disease or a mammogram does for detecting breast cancer: an inexpensive, replicable and reliable test that could tell the public their risk for developing PD,” Stern said.

PD is a neurodegenerative disease most known for its physical signs including tremors, rigidity, and a loss of balance resulting from the slow death of the neurons in the brain that produce dopamine, the neurotransmitter that signals movement and coordination. As dopamine diminishes, symptoms worsen.

The most predictive test currently available is a smell test: researchers have found that a loss of a sense of smell can be an early indicator of neurodegeneration in PD. Stern and colleagues created the Parkinson’s Associated Risk Study (PARS) and sent smell tests to 10,000 subjects, some with a family history of PD, many without, and followed them over the ensuing five years to see if they could detect early signals of the disease that might predict an increased risk for developing PD.

Researchers then teased out a small group of 300 subjects; 200 who had a markedly abnormal sense of smell and a control group of 100 subjects whose results showed a normal sense of smell. They tested the levels of dopamine in the brains of all 300 patients using a dopamine transporter scan and found that 11 percent of patients who reported a diminished sense of smell also had a dopamine deficit, compared with only one percent of subjects in the normal-smelling group. The researchers also found that 61 percent of the patients with dopamine deficits developed PD within four years. The results were presented in June at the International Congress of Parkinson’s Disease and Movement Disorders in Berlin, where the group was recognized for their “blue ribbon” research, giving the PD research community new insights into PD diagnostics.

“We are beginning to see that much of the pathological damage is done by the time symptoms are apparent,” Stern said. “If we know the early signs of risk, we can begin treatment and we hope, stave off the development of the disease and eventually prevent it from developing at all. We need to get at the disease before it is too late to reverse the damage.”

For the time being Stern and colleagues have become very good at using the available medications to treat the motor symptoms of PD. But, the damage is not just physical.

Over time, 80 percent of PD patients will also experience some cognitive loss and a large proportion of patients will eventually develop dementia. Researchers at Penn’s prestigious Udall Center for Parkinson’s Research studies the cognitive effects of the disease. Under the leadership of John Trojanowksi, MD, PhD, the William Maul Measey-Truman G. Schnabel, Jr., MD professor of Geriatric Medicine and Gerontology, and a professor of Pathology and Laboratory Medicine, Udall researchers are collecting blood, plasma, cerebrospinal fluid, genetic information and brain imaging from patients to try to determine markers for cognitive decline and impairment in PD. Using these fluids, they are making great strides in being able to predict which patients will develop dementia, which has the potential to lead to better treatments for the cognitive impact of PD. In fact, Penn is currently participating in the first-ever clinical trial of a new drug to treat the cognitive symptoms of PD. “This is a major unmet need in the treatment of PD,” Stern said.

PD, along with similar neurodegenerative conditions, can also be accompanied by a lack of motivation, organization, planning and even depression. While it is not entirely known why this develops, Nabila Dahodwala, MD, MS, an associate professor of Neurology, is looking at ways to help her patients overcome it. She is in the process of developing a smartphone app that will remind and motivate patients to complete designated tasks and meet specific goals – which can include things like exercise and social engagement – between their appointments.

Finally, Dahodwala and Meredith Spindler, MD, an assistant professor of Clinical Neurology, are two Penn practitioners looking out for the caregivers of patients with PD. Dahodwala is an advocate for more formal support systems for caregivers. “Improved care for caregivers can lead to better patient care, quality of life and rates of survival,” she said.

Spindler is looking to technology to ease the burden on patients and caregivers alike through telemedicine. As her examination of patients is primarily visual, Spindler is taking advantage of advancements in telemedicine and has begun to “see” patients by video, relieving patients and caregivers from traveling to and from her office. “We are increasingly looking at ways to improve care delivery,” Spindler said.

Stern, who founded Penn’s PD and Movement Disorders Center in 1982 along with Howard Hurtig, MD, now an Emeritus professor of Neurology, has seen great changes in PD treatment and research over the last 34 years. He is hopeful that within the next decade, researchers will really move the needle to a place where early diagnosis and detection is readily available so that clinical trials of disease delay or prevention will help make a meaningful impact on the natural history of this disease.


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