The search for a Parkinson’s disease biomarker

Our A Closer Look blog is designed to educate, inform, and inspire you through a variety of topics and insights about Parkinson’s disease (PD). One way we do that is through our Interview with APDA Researchers series within this blog so you can get a closer look at some of the dedicated APDA-funded researchers who are working tirelessly to understand this disease.

Today we introduce you to Dr. Mohammad Shahnawaz, Assistant Professor of Neurology at the University of Texas Health Science Center at Houston. His current research focuses on identifying the underlying mechanisms that cause Parkinson’s disease and other neurodegenerative disorders, and developing early biomarkers for these diseases.

Q: What is the overarching goal of your research? What do you hope to find out?

A: Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative disorders in which normal proteins misfold and build up in the brain in the form of aggregates or clumps. These protein clumps interfere with the normal functioning of the brain cells, eventually causing cell death. The process of misfolding is believed to start years or decades before the appearance of clinical symptoms of AD or PD. Interestingly, these misfolded proteins can also be found in body fluids such as cerebrospinal fluid (CSF) and blood, before clinical symptoms develop, and therefore may be able to be used as biomarkers for early diagnosis of these diseases. However, despite extensive research, there is no reliable laboratory test available yet that can detect these abnormal proteins in body fluids.

My current research goal is to detect misfolded proteins in blood so that a non-invasive and low-cost diagnostic test can be developed for these diseases. Furthermore, I am trying to understand the molecular mechanisms by which these misfolded protein clumps contribute to cell death. I am exploring the pathological functions of misfolded proteins that are isolated from the brains of patients with AD and PD. I hope my research findings will not only help in the development of early blood-based diagnostic tests for these diseases, but will also help us understand the important roles abnormal proteins play in these diseases.

For a while now, I have been fascinated by the intriguing features of a group of diseases known as prion diseases. In this set of diseases, it is thought that misfolded proteins convert normal proteins to abnormal forms to cause disease. Now, some research suggests that this phenomenon is responsible for the protein misfolding of AD and PD as well, highlighting the importance of abnormal proteins as potential biomarkers and the role they play in these diseases.

Q: Could you describe how you perform your studies?

A: The quantities of abnormal proteins present in body fluids that we are trying to detect are too low to be detected effectively and reliably by currently available methods. For that reason, we have adapted a test called the Protein Misfolding Cyclic Amplification (PMCA) assay in our laboratory, which has long been used for detecting abnormal proteins associated with prion diseases. In a PMCA assay, a sample of either blood or CSF, that may or may not contain misfolded proteins, is mixed with normal proteins in defined experimental conditions. We then monitor whether the misfolded protein causes the normal protein to misfold, which can be easily detected using fluorescent dye.

 Q: Can you tell us a little bit about what you have found out so far?

A: Recently, using the PMCA assay, we have been able to detect small amounts of abnormal protein in cerebrospinal fluid (CSF) samples from patients clinically diagnosed with AD and PD, with high sensitivity and specificity. There is more misfolded protein in CSF than in blood, which makes it easier to use for detection. However, the collection of CSF is more invasive than a blood test (CSF samples are obtained via a needle inserted into the fluid surrounding the spinal nerves that emerge from the bottom of the spinal cord). We are currently testing several different approaches in our laboratory to figure out how to perform these tests successfully in blood.

Q: What fuels your passion for neurodegenerative disease research?

A: My research is a great opportunity for me to make valuable contributions to the understanding of these diseases by developing early diagnostic tests and by exploring the roles of abnormal proteins. I truly believe that early diagnosis means better treatment and better disease management.

Tips & Takeaways:

• Important PD research is constantly taking place across the APDA network.
• Shahnawaz is a recipient of an APDA research grant for the 2019-2020 academic year. Read more about all of the current research APDA is funding.
• His research is largely focused on creating a non-invasive and low-cost blood-based diagnostic test for PD.
• We are only able to fund this research because we receive donations from dedicated people like you. If you would like to support this critical work, please consider making a donation