Study Rationale:
Parkinson's disease (PD) is characterized by both motor symptoms and non-motor symptoms. While progress has been made in addressing motor symptoms, non-motor symptoms remain a critical unmet need. These include cognitive impairment, behavioral disorders, neuropsychiatric issues and sleep disorders, which severely impact quality of life. Our research explores novel approaches to address these underserved aspects of PD by evaluating our investigational candidate compound in pre-clinical models exhibiting these symptoms.
Hypothesis: We hypothesize that our candidate compound will influence behaviors and physiological indicators related to non-motor symptoms in a preclinical PD model, and that examining the compound's mechanism of action will provide insights for translational research, potentially bridging the gap between preclinical findings and clinical applications.
Study Design: We will evaluate our investigational compound using three pre-clinical PD models to assess its therapeutic potential on both motor and non-motor symptoms. One model relies on injection of preformed alpha-synuclein fibrils; another uses virus-mediated production of mutant alpha-synuclein; the third employs chemical induction of neurodegeneration. In all three models, we will comprehensively evaluate both motor and non-motor symptoms, including anxiety, cognitive function and sleep dysfunction. To elucidate the compound's mechanism of action, we will also analyze brain volume changes using MRI and quantify specific neuronal populations, accumulation of phosphorylated alpha-synuclein, key pathological biomarkers and neuroinflammatory markers.
Impact on Diagnosis/Treatment of Parkinson’s disease: This research addresses the critical unmet needs in treating the non-motor symptoms of PD, which currently lack standard treatment options. Our aim is to support research that could lead to comprehensive management strategies for PD, improving individuals’ overall quality of life.
Next Steps for Development: Following completion of initial safety studies, subsequent research will evaluate responses in individuals with neurodegenerative conditions experiencing non-motor manifestations.