Free Water Levels Provide a New Biomarker for Parkinson’s Disease Progression

Iqra Mumal, MSc avatar

by Iqra Mumal, MSc |

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Free Water Level factor in Parkinson's disease

According to a recent study, a newly discovered biomarker, free water, can track changes in the brain that are associated with Parkinson’s disease, which ultimately may aid in developing new drugs that could slow disease progression.

“This finding is a potential game changer as it could shift the way Parkinson’s disease clinical trials are designed and conducted,” said Michael S. Okun, MD, a professor and chair of neurology at the University of Florida and medical director for the Parkinson’s Foundation. “Free-water is a validated measurement that will likely decrease the number of patients required to demonstrate the slowing of clinical progression.”

The study titled, “Progression marker of Parkinson’s disease: a 4-year multi-site imaging study,” was published in the journal Brain.

One of the issues in developing disease-modifying therapies for Parkinson’s disease has been a lack of an accurate biomarker that can detect changes in the brain as the disease progresses. Recently, a new imaging technique was developed that can accurately detect the volume of water in brain tissue and separate that measurement from the water outside the brain tissue. The latter type of water is known as free water and has been known to increase in neurodegenerative disorders.

In 2015, researchers demonstrated that free water levels were increased in the posterior substantia nigra (PSN) of patients with Parkinson’s disease. The motor symptoms that accompany a diagnosis of Parkinson’s disease tend to emanate from the area of the brain that includes the nigrostriatal pathway, which is part of PSN.

In another study, researchers discovered that the free water levels in the PSN increased over one year in newly diagnosed Parkinson’s disease patients, but not in control groups. However, no studies have investigated how free water in the PSN changes over an extended period of time.

Therefore, researchers at the University of Florida conducted a multicenter international longitudinal study to determine the pattern of change in free water in patients with Parkinson’s disease over four years.

Results from this study showed that free water levels in PSN increased over one year in newly diagnosed Parkinson’s disease patients. Furthermore, free water levels continuously increased over four years. The research team also showed that sex and baseline free water predicted four-year changes in free water levels. Additionally, researchers showed that free water increasing over one or two years leads to worsening stages on the Hoehn and Yahr scale over a four-year period.

One of the most important things to result from this study has been the discovery of a biomarker that determines the progression of Parkinson’s disease and one that can potentially be used in future clinical trials as an endpoint.

“This means if you want to start designing studies to slow the progression of Parkinson’s disease, testing a drug on that measurement in the substantia nigra might be a good way to go,” said David Vaillancourt, PhD, professor of applied physiology and kinesiology at the University of Florida in a press release. “If the measurement in the substantia nigra is increasing year after year after year, and if you can stop that from occurring, you’re likely to slow or possibly stop the progression of the disease. This could change the way studies are conducted for disease-modifying trials in Parkinson’s disease.”


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