Evaluation of mitochondrial function in skin fibroblasts as a biomarker for the efficacy of two physical activity programs in Parkinson's disease patients

Introduction: Parkinson's disease (PD) is a disorder characterized by the progressive degeneration of dopaminergic neurons resulting in dopamine deficiency in the striatum [1]. Mitochondrial dysfunction and oxidative stress are associated with PD and are intrinsic factors related to its pathogenesis. Physical activity (PA) increases cognitive ability in older adults, attenuating motor deficits, increasing new neuron formation, ameliorating neurological impairments, and impeding age-related neuronal loss [2]. In addition, skin fibroblasts have been identified as surrogate indicators of pathogenic processes correlating with clinical measures [3,4]. Thus, the present study aims to compare the effects of two different PA programs in PD patients analyzing relevant clinical aspects and the impact on mitochondrial function in patients' skin fibroblasts, used here as biomarker for metabolism improvement and disease progression.
Methods: Patients with early-stage PD (stage I to III, according to the modified Hoehn-Yahr classification; n=24) will be recruited and randomized into three matched groups. The effects of two different PA programs will be compared. The first group (n=10) will perform basic physical training (BPT) based on strength and resistance; a second group will perform BPT combined with functional exercises (BPTFE), including exercises aimed to stimulate the specific sensorimotor pathways that are most affected in PD (proprioception-balance-coordination) together with cognitive and motor training; a third group will serve as control (sedentary group; Sed). Subjects will perform 3 sessions per week for 16 weeks. Motor function, quality of life, sleep quality, cognitive aspects and humor will be evaluated before and after intervention. A metabolic characterization of skin fibroblast will be performed by respirometry using the Seahorse XFe96, and by measuring ATP levels and mitochondria-related transcripts and proteins to determine the bioenergetic cellular deficits and characterize the metabolic remodeling induced by the exercise programs.
Results: We predict that the application of BPT and BPTFE programs will ameliorate relevant clinical aspects of the disease by improving systemic mitochondrial function, restoring mitochondrial metabolism, gene expression patterns, and ultimately, translating into mitochondrial neuroprotective effects.
Conclusions: The comparison of BPT and BPTFE PA programs will provide insights into the degree of amelioration in several relevant aspects of PD, including motor function, quality of life, quality of sleep, cognitive aspects, humour, and mitochondrial function. Such changes can have a positive clinical impact and PD skin fibroblasts may be used as a biomarker for PD diagnosis and disease progression