The U.S. Defense Department has awarded researchers from Northeast Ohio Medical University (NOMU) and Michigan State University (MSU) about $1 million each to study the effect of exercise at different stages of Parkinson’s disease.
The three-year grant went to longtime collaborators Sheila Fleming, PhD, an assistant professor of pharmaceutical sciences at NOMU and Caryl Sortwell, PhD, a translational neuroscience professor at MSU.
“It’s a major award for both of us,” Fleming said in a news release. “We had been working together for many years because our interest and work are very complementary. Ultimately, it’s about a $2-million grant. She gets half and I get half.”
Fleming, who was awarded $954,566 by the U.S. Army Medical Research Acquisition Activity, said she will work on behavioral aspects of the study while Sortwell will handle pathological events.
The project, titled “Exercise Effects on Synuclein Aggregation, Neuroinflammation and Neurodegeneration,” will analyze the impact of exercise in an optimized preclinical disease model. That will include examining mechanisms associated with the central characterization of Parkinson’s — the buildup of toxic alpha-synuclein aggregates, neuroinflammation, and expression of certain molecules in the brain called trophic factors.
Using a progressive Parkinson’s disease animal model, Sortwell is charting the course and development over time of pathological events in the brain. Fleming is examining how the pathological occurrences relate to changes in motor and non-motor symptoms. Together, the researchers are examining the impact of introducing exercise at different stages of Parkinson’s progression.
Most scientists studying exercise in Parkinson’s have used what are called toxin models, which solely target the dopamine system, Fleming said. The chemical dopamine acts as a neurotransmitter and is essential in sending messages from the brain to direct muscle movement and coordination. As more dopamine-producing neurons die, dopamine levels slowly and progressively decrease until patients are unable to control normal movements.
But those models have issues related to reproducibility and a lack of understanding of the biological properties of alpha-synuclein pathology. Fleming and Sortwell are using a newer model supported by the Michael J. Fox Foundation called PFF — for pre-formed synthetic fibrils — to elucidate mechanisms of alpha-synuclein-induced pathology. In this model, fibrils are injected into animals, and researchers track the appearance of symptoms.
Studies have already shown the likelihood that alpha-synuclein clumping begins in the back of the brain and proceeds to the front, a pathology that may be related to non-motor Parkinson’s symptoms such as depression, anxiety, reduced sense of smell, and cognitive impairment.
Fleming and Sortwell will look at the effect of exercise on both non-motor and motor symptoms (such as problems walking) to determine what symptoms manifest and in what order. This information could lead to earlier diagnoses, and provide a non-pharmacological, low-cost therapeutic strategy for patients, including veterans.
Currently, Fleming said, by the time individuals first seek help for symptoms, they have typically already lost at least half their dopamine neurons.
“Slowing the progression of the disease could have a huge benefit, especially since patients aren’t usually diagnosed until between 50 and 60 years of age,” she said. “So, if you could slow it, that could have a potentially huge impact on the quality of life of patients.”
The scientists presented their project in October at the annual meeting of the Society for Neuroscience.