Study Rationale: NOD2 is a key component of our immune defense system that detects invading pathogens and promotes their removal. Under healthy, ideal circumstances, NOD2 activity has a ‘Goldilocks-like’ balance; not too active or too inactive, but just right. However, when NOD2 becomes dysregulated (either overactive or repressed), it leads to diseases, including increased risk of developing Parkinson’s disease (PD). However, in patients with PD, we currently do not know if this change is due to overactive or repressed NOD2 function.
Hypothesis: To consider NOD2 as a new target for PD (as proposed through MJFF's T2T Initiative), we need to know, should we increase or suppress NOD2 in patients with PD as a potential new therapeutic option to slow down their disease progression?
Study Design: Many other diseases have known loss of NOD2 normal function, such as patients with Blau Syndrome (increased NOD2 activity) and genetic forms of Inflammatory Bowel Disease (decreased NOD2 activity). We will identify NOD2-related genes and pathways that are shared between these diseases based on genetic and molecular patient data analyses. Using these results, we will combine evidence to make a prediction on if NOD2 should be activated or inhibited for therapeutic benefit in patients with PD and determine if there are differences in which way we should modulate NOD2 in different cell types.
Impact on Diagnosis/Treatment of Parkinson’s disease: Our study aims to clarify how NOD2 could be modulated as a new way to treat patients with PD.
Next Steps for Development: Once we have added confidence in how to correct dysfunctional NOD2 activity in patients with PD, we can use this information to inform what type of NOD2 drug we should create as a new PD therapy.