Your genetic makeup is a like a fingerprint for your health. Differences (variations) in your genes are what make you unique. But inherited gene changes and mutations also affect your genetic predisposition (likelihood) of developing a disease.
People with Gaucher disease have two mutations in the GBA gene (carriers have one). But mutations in the GBA gene are also associated with other diseases. Up to 15% of people diagnosed with Parkinson’s disease have a GBA gene mutation. Parkinson’s disease is a neurological disorder that primarily affects older adults. It impacts the nervous system and the body’s ability to move. A GBA gene mutation is the most common genetic risk factor for Parkinson’s disease.
But it’s not the only connection between Gaucher disease and Parkinson’s disease, according to Robin Ely, MD, a founding member of the National Gaucher Foundation (NGF). Dr. Ely currently serves as the Clinical Director for NGF and practices integrative medicine. She approaches health and wellness from all angles, considering each person’s mind, body, and spirit.
Parkinson’s disease and Gaucher disease have something else in common: they are both inflammatory conditions. Dr. Ely believes underlying inflammation may be an important piece of the Parkinson’s puzzle. Managing inflammation may help reduce the risk of Parkinson’s disease for people living with Gaucher disease.
The Role of Inflammation in Parkinson’s Disease
People with Parkinson’s disease often have elevated levels of a protein in the brain called alpha-synuclein. Parkinson’s research often focuses on reducing or preventing alpha-synuclein accumulations.
“People have tried lowering alpha-synuclein with antibodies and other methods for years. It hasn’t panned out,” Dr. Ely says. “But experts recently recognized that underlying inflammation may be behind alpha-synuclein build-up.”
Chronic inflammation triggers a set of symptoms (inflammatory response). Every person reacts differently to inflammation. Your body’s response to chronic inflammation depends on your:
- DNA code: Your unique genetic makeup.
- Epigenetics: Your exposure to environmental contaminants (such as pollution, tobacco, and toxic chemicals) that affect how your genes function.
“In some individuals, the body’s response to inflammation can cause certain proteins to accumulate,” Dr. Ely says. “If your inflammatory response causes alpha-synuclein to build up, the accumulation interferes with how your brain communicates with certain areas of the body. The result is symptoms associated with Parkinson’s disease.”
Those symptoms can trigger an inflammatory response. It’s an endless loop.
Inflammation in Gaucher Disease and the Risk of Parkinson’s Disease
People living with Gaucher disease are susceptible to systemic inflammation. When your immune system is constantly defending your body—as happens with many chronic diseases—it enters a pro-inflammatory state. That means the immune system is always working and ready to pounce, causing immune responses that may be more intense and last longer.
“Think about your inflammation like a burner that’s on simmer. In any chronic condition, it’s a matter of turning the flame up or down. But the flame is always there,” Dr. Ely says. “That ongoing inflammation in genetically predisposed individuals can, over time, trigger the development of Parkinson’s symptoms.”
Does Gaucher disease treatment help with inflammation?
About 9% of people with Gaucher disease will develop Parkinson’s disease. Whether you undergo Gaucher disease treatment doesn’t appear to be a factor. Enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) greatly reduce the non-neurological symptoms of Gaucher disease, which may include inflammation. But the treatment doesn’t reduce the risk of Parkinson’s disease.
“Enzyme therapy does work, but it doesn’t work totally,” Dr. Ely says. “It doesn’t completely remove all the symptoms. A chronic, low level of inflammation is triggering the symptoms that remain. It’s always simmering, creating symptoms such as achiness and fatigue.”
Do Gaucher disease carriers experience underlying inflammation?
Carriers of Gaucher disease only have one GBA gene mutation. The mutation does not cause Gaucher disease symptoms in carriers. But the gene is still defective and not functioning as it should.
“In people who are carriers, the pilot light is still on, and they likely have a very low level of underlying inflammation,” Dr. Ely says. The underlying inflammation may not be bothersome or even noticeable. But it still increases the risk of Parkinson’s. Gaucher disease carriers have a low risk of developing Parkinson’s disease (3%), but it is still higher than average (<1%).
Studying the Connection Between Gaucher Disease and Parkinson’s Disease
Parkinson’s may be the most rapidly increasing neuroinflammatory disorder globally, according to Dr. Ely. Clinical and academic researchers are working to address the inflammatory response and imbalances that are triggering symptoms.
Researchers also continue to explore the link between alpha-synuclein and glucocerebrosidase (GCase)—the enzyme associated with Gaucher disease. Many studies show that decreased GCase activity impacts the accumulation of alpha-synuclein. But further research is necessary to understand the relationship and its full impact.
“More and more experts are realizing that there is no one size fits all when it comes to treating inflammatory conditions,” Dr. Ely says. “In this era of personalized medicine, how we address targets within the neuroimmune system has to be integrated and individualized.”
The Takeaway for People Who Have Gaucher Disease or Are Carriers
Taking steps to reduce inflammation is critical if you have Gaucher disease or are a carrier—even if you are undergoing treatment for Gaucher disease.
But it’s not only about managing Gaucher symptoms. It’s also about reducing the risk for Parkinson’s disease and other neurodegenerative disorders associated with low, ongoing inflammation.
Many of your everyday choices and behaviors affect your immune system. That means that small lifestyle changes can help manage inflammation. Consider taking steps to improve your:
“Learn as much as you can about managing inflammation,” Dr. Ely says. “Having that knowledge will help you be proactive about your health and motivated to make those lifestyle changes.”
How the National Gaucher Foundation Can Help
If you or a loved one lives with Gaucher disease, the National Gaucher Foundation is here for your family. We offer resources to optimize your health with Gaucher disease and connect you with the support you need.
- Cells—GBA Variants and Parkinson Disease: Mechanisms and Treatments—https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029385/#:~:text=Approximately%205–15%25%20of%20PD,for%20Parkinson%20disease%20(PD).
- J Neural Transm—Epidemiology of Parkinson’s disease—https://pubmed.ncbi.nlm.nih.gov/28150045/
- J Parkinsons Dis—GBA1 and the Immune System: A Potential Role in Parkinson’s Disease?—https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9535551/