Can the gut help us understand Parkinson’s disease?: A Q&A with Dr. Ehraz Anis

At first glance, the gut and the brain may seem vastly different, but they share many similarities that may have major implications for health. One example is Parkinson’s disease.

Most people think of the brain when they think of Parkinson’s, but it turns out that the gut may also play an important role. That’s because the gut, like the brain, is full of nerves and chemical messengers that help us respond to the world around us and within us. Additionally, some of the earliest symptoms of Parkinson’s, which may appear years before diagnosis, affect the gut.

Dr. Ehraz Anis

Ehraz Anis, Ph.D., a postdoctoral fellow in the laboratory of Lena Brundin, Ph.D., is exploring how this link may influence Parkinson’s in hopes that it may lead to new ways to detect the disease.

VAI Voice caught up with Dr. Anis to discuss how the appendix may impact Parkinson’s and what this research may mean for the future.

What do you study?

EA: We study the link between the gut and the brain in the context of Parkinson’s disease.

We focus on the vermiform appendix, which has classically been considered an organ that doesn’t have much use in modern humans. In the late 2000s, a study showed that the appendix plays a role in how our body reacts to infection and is not a ‘vestigial organ,’ or an organ that no longer has any real purpose, as previously accepted. Additional studies have shown that the appendix actually plays a role in immunity and maintaining digestive health.

In a 2018 epidemiological study, a team led by scientists here at Van Andel Institute found that having the appendix removed is associated with an approximately 20% lower risk of developing Parkinson’s disease, hinting toward a link between the appendix and the brain.

Our current work is based on this study, and we are trying to decipher what could go wrong inside the appendix that could lead to the possible development of Parkinson’s disease.

What are some questions you’re hoping to answer with your research?

EA: We are starting at the very beginning since the appendix has not been explored much at a molecular level — especially in the context of neurodegenerative disorders such as Parkinson’s disease.

We use a test called the seed amplification assay (SAA) to understand how a misshapen protein called alpha-synuclein may push normal, healthy proteins to transform into abnormal shapes. Proteins are the workhorses of the body and are responsible for virtually every biological process. Their ability to do their jobs correctly is tied to their shape. When they become misshapen, they no longer function properly and can cause problems. In Parkinson’s, it is believed that these misshapen proteins clump together and clog up cells, which eventually kills them. The result, we believe, are Parkinson’s symptoms.

To visualize this change from a healthy protein to a misshapen one, think of a drop of ink spreading through water. The water starts out clear, but once a drop of ink comes in contact with it, the clear water starts turning into the color of the ink. This protein, alpha-synuclein, is relevant for our study because it is found in certain brain regions of people with Parkinson’s disease.

In addition, we also want to find out if inflammation in the appendix can change the rate of this conversion from normal to pathological, which would point toward an increased likelihood of developing disease. We also will characterize the pathological forms of this protein and see how they differ from the normal protein. Finally, we will look at the changes happening at the gene level that could also play a part in development of disease. Fitting together all these pieces will give us a much better look at the bigger picture.

Why is this work important?

EA: Understanding how Parkinson’s starts and how it progresses is important for developing new ways to diagnose and treat the disease.
If we are able to compare the rate of this conversion from normal to pathological protein in appendix tissue from different patients, we could potentially tell which of them are more likely to exhibit the disease-causing changes.

Appendix removal, or appendectomy, is one of the most common emergency surgical procedures performed in the United States, with around 300,000 surgeries performed every year. Most people who undergoing the procedure leave the hospital within a couple of days to recover at home. Furthermore, with medical advancement, appendectomies have become minimally invasive, which means it would be relatively easy to get tissue for biopsy. As of now, pathological changes in the brain cannot be examined at a molecular level during a person’s life so we need to find other ways to objectively diagnose the disease. Right now, this is done by reviewing their medical history and physical exams. With some standardization of the SAA for appendix tissue, our study could potentially lead to development of a simple method of screening for Parkinson’s disease. This will be especially important if we also can develop new treatments that slow or stop disease progression, which is not possible with existing therapies.

What comes next?

EA: We are working hard toward standardizing the procedure and adapting it to work with appendix tissue. Once we are done with that, we can confirm that our findings are accurate by comparing data from our experiments at the genetic level. When our findings are corroborated, we can continue to refine the procedure to increase its sensitivity and specificity, which would decrease the chances of getting false positive and false negative results. We could also adapt this procedure for other types of tissues or bodily fluids, to come up with further confirmatory tests. Since there is no way to cure Parkinson’s disease right now, the best thing we can do is come up with a way to detect it early and try to stop or slow down its progression.

Research reported in this publication was supported by Van Andel Institute and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award no. R01NS114409 (Brundin). This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.