Study Rationale:
Parkinson’s disease is characterized by premature death of dopamine-producing neurons in the brain; cancer is characterized by overgrowth of dividing cells. Despite being very different, Parkinson’s disease and cancer both have immune dysfunctions. Cancer occurs when the immune system fails to safeguard, and immune therapy holds new hope for cancer treatment. Parkinson’s disease has also been related to immune dysregulation. Moreover, Parkinson’s disease and cancer can in fact be caused by the same gene alterations. Two genes, LRRK2 and Parkin, are among such genes.
Hypothesis:
We bring together a team of experts in the fields of Parkinson’s disease and cancer to borrow sophisticated approaches from cancer research to collaboratively test a hypothesis that immune dysregulation is the reason why alterations in LRRK2 and Parkin can cause both Parkinson’s disease and cancer, with a focus on Parkinson’s disease in this proposed work.
Study Design:
We will use dopamine-producing neurons derived from Parkinson’s disease patient stem cells and mouse models with genetically modified LRRK2 and Parkin to modulate and characterize immune signatures in both the periphery and the brain. In addition, we will perform immune profiling in samples from patients with Parkinson’s disease or cancer.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
The proposed work approaches Parkinson’s disease from a unique angle. The findings will help better understand common molecular mechanisms underlying Parkinson’s disease and cancer. Immune-related molecules and pathways identified may become new therapeutic targets for Parkinson’s disease.