Meet a Researcher Working to Link Parkinson’s, Genetics and the Immune System
For decades, we have known that inflammatory changes occur in the brain of people with Parkinson’s disease (PD). But in the last few years, inflammation has been studied as a possible cause of the progressive nature of the disease and not just a result of it.
Catherine (Chi) Weindel, PhD, is studying this connection, specifically focusing on how one variant or mutation of the Parkinson’s disease-linked gene LRRK2 impacts immune health. She hopes this research will pave the way for a deeper understanding of how Parkinson’s starts and progresses, along with avenues for potential new therapies.
LRRK2 and PD
The LRRK2 gene plays a role in about 1% of all people with PD and 5% of those with a family history. LRRK2 variants are autosomal dominant — this means that inheriting only a single mutated copy of a gene from one parent can potentially lead to disease. Mutations in LRRK2 can result in the enzyme becoming overly active in the brain, leading to cell death in ways we do not yet fully understand.
“My research involves the study of the immune system. What I am interested in is determining how the immune system might be different in people with Parkinson’s genetic mutations, which would cause a difference during an infection or in response to an environmental toxin,” said Dr. Weindel. “I am studying how alterations or modulations in an immune response could build up over time, piece by piece, and might predispose someone to develop Parkinson’s later in life.”
When Dr. Weindel first began investigating Parkinson’s, she suspected that immune system inflammation, triggered by illnesses and loss of dopamine neurons outside the
brain, could ultimately lead to the development of the disease. This line of thinking led to her Parkinson’s Foundation Postdoctoral Fellowship, where she designed a study to explore how a LRRK2 G2019S mutation may impact mitochondria, which provide energy for a cell, when immune cells have been stressed by infection.
She discovered that during an infection, when immune cells with LRRK2 mutations die, they uniquely increase inflammation that promotes the spread of bacteria throughout the body. This cell death seems similar to what researchers find in brains of people and mice with PD.
Now, as a 2022 Parkinson’s Foundation Launch Award recipient, Dr. Weindel is taking her research a step further to gain a deeper understanding of how LRRK2 gene mutations cause cell death in immune cells in the brain. This will lead to the identification of new targets for Parkinson’s therapy that may better control inflammation, for instance. Her research will also help design improved genetic tests to give families with a history of Parkinson’s better insight into their risk for developing PD.
According to Dr. Weindel, genetics research is vital to understanding the connection between Parkinson’s disease and the immune system’s response because even when family members have the same PD mutation, the disease may present itself differently in each person. By looking at complex genetic interactions, we can see alternative pathways impacting specific individuals, which can dictate better clinical trials or potential therapies.
“My goal is to develop therapeutics that will allow for a more personalized medical approach,” Dr. Weindel said. “Because Parkinson’s is such a diverse disease, a cure-all is very unlikely. Ideally, a particular therapeutic can one day be designed for an individual based on the genetic makeup of their Parkinson’s.”
Explore ongoing Parkinson’s Foundation research, including our landmark genetics study, PD GENEration at Parkinson.org/PDGENEration.