PROJECT SUMMARY/ABSTRACT
Despite advances in pharmaceutical and surgical approaches to the treatment of Parkinson’s disease (PD), an
effective disease modifying treatment remains elusive. A growing body of evidence supports the notion that
high intensity aerobic exercise, when delivered in a highly supervised, well-controlled laboratory setting,
improves PD symptomology. Despite community exercise being recommended by the American Physical
Therapy Association, high intensity aerobic exercise performed in a community-setting is not supported by third
party payors and therefore not delivered by physical therapists. The aim of this project is to address two
fundamental gaps related to the widespread utilization of exercise to modify PD: 1) are community-based
exercise programs effective in altering disease progression? and 2) what is the role of genetics in modulating
the disease altering effects of high intensity aerobic exercise? Our underlying hypothesis is that high-intensity
community-based exercise is effective in slowing disease progression in PD and those positive effects are
more likely to occur in individuals with a lower genetic\biological burden. The proposed multi-site, Genetics and
Aerobic Exercise to Slow (GEARS) PD trial will determine the interplay between genetics and exercise in
altering PD progression. A total of 250 individuals with PD will be enrolled in Pedaling for Parkinson’s (PFP)
programs across six locations in NE Ohio and Salt Lake City. The PFP exercise protocol is rooted in our
established and effective laboratory-based exercise protocol for PD (e.g. exercise at 60-80% of heart rate
reserve and strive to pedal at 75 RPMs). The PFP community group will exercise 3 times per week for 12
months. A novel and efficient aspect of the GEARS Trial is the leveraging of PD control data (n=125) from Dr.
Alberts’ CYCLE-II RCT (2R01NS073717; enrollment completed March 2022). Identical clinical and
biomechanical data characterizing motor and non-motor function will be gathered from the PFP group to match
historical control outcomes. Genetic burden for PD will be determined for all 375 PD patients by determining
the PD polygenic risk score. Aims 1-3 will determine the disease altering potential of community-based
exercise using clinical and biomechanical outcomes reflective of motor and non-motor performance. A
prognostic model will be developed in Aim 4 to predict what factors are important in modulating the beneficial
effects of exercise on slowing disease progression. The model will facilitate understanding of the interplay of
genetics, aerobic exercise, and disease progression and serve as a non-incremental step in the development
of patient-specific exercise recommendations in which potential outcomes can be estimated. Demonstrating
the effectiveness of a community-based exercise program, that can be scaled for minimal cost, will bring an
effective intervention to PD patients that is not impacted by the healthcare reimbursement policy and politics.
