Study Rationale: Approximately 16.5 million people have been infected with the SARS-CoV2 virus. While primarily a respiratory virus, clinical observations indicate that in many cases, infection is associated with nervous system involvement, including the central nervous system (headache, confusion, seizure and stroke), peripheral nervous system (pain, loss of smell and taste) and enteric nervous systems (diarrhea). This preclinical study will examine whether, and how, the acute and longer-term effects of SARS-CoV2 infection may contribute to the onset and development of PD pathology.
Hypothesis: We hypothesize that infection with SARS-CoV-2 will accelerate the progression and sequalae of alpha-synuclein pathology in the brain region affected by PD, and that these effects will be further aggravated in a preclinical PD model bearing the G2019SS LRRK2 mutation.
Study Design: We will inject preformed fibrils of human alpha-synuclein into the brains of mice infected with the B1.1.17 strain of SARS-CoV-2 (COVID-19). After 30 or 60 days, we will map the deposition of alpha-synuclein aggregates and the pathology it induces, including inflammation and cell death. We will also infect mice carrying a mutant LRRK2 (G2019S KI) with COVID-19 and explore whether these two insults synergize to increase neuronal cell death and inflammation.
Impact on Diagnosis/Treatment of Parkinson’s disease: If we find that COVID-19 infection increases parkinsonian pathology, we can determine whether vaccination alters this effect. We can also potentially prepare for the possibility of a future increase in parkinsonism secondary to COVID-19 infection.
Next Steps for Development: If we find that COVID-19 accelerates parkinsonian pathology in preclinical models, we can examine the ability of a variety of interventions (including vaccine, anti-virals or LRRK2 kinase inhibitors) to modify these synergistic interactions.