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A newly discovered imaging biomarker could be used to track changes in the brain associated with the progression of Parkinson鈥檚 disease, findings that represent a significant advancement that could aid in development of new drugs to slow progression of the neurodegenerative disease.

The team of University of Florida neuroscientists who made the discovery has validated the finding in data collected as part of an international multicenter study published in the current issue of the journal Brain. The study shows that on diffusion MRI scans there is an increase over one year in 鈥渇ree-water,鈥� or fluid unconstrained by brain tissue, in a part of the brain called the substantia nigra in a large cohort of more than 100 newly diagnosed, unmedicated Parkinson鈥檚 disease patients. This change is not seen in people without Parkinson鈥檚.

Additionally, in a subgroup of Parkinson鈥檚 disease patients who have been followed for up to four years across Europe and North America, analysis of the diffusion MRI data revealed that free-water in the posterior substantia nigra continued to increase.

Use of this noninvasive biomarker tool could lead to new ways of testing treatment of the progressively debilitating movement disorder, said senior author , a professor of applied physiology and kinesiology in , and a member of the .

鈥淭his could change the way studies are conducted for disease-modifying trials in Parkinson鈥檚 disease,鈥� Vaillancourt said.

Until now, Parkinson鈥檚 disease has generally been diagnosed based on a patient鈥檚 symptoms.

鈥淚t鈥檚 been 200 years since the behavioral symptoms of Parkinson鈥檚 disease have been described, and we still use symptoms in testing therapies,鈥� he said. 鈥淭his is not the way it occurs in cancer; it鈥檚 not the way it occurs in heart disease or multiple sclerosis. But symptoms are still the hallmark of what鈥檚 used in Parkinson鈥檚 disease because there are few options out there.鈥�

Now, this could change.

Two years ago, Vaillancourt鈥檚 team published findings based on a type of MRI technique known as diffusion MRI that revealed changes in free-water in the posterior substantia nigra that are specific to Parkinson鈥檚 patients. Now, the team鈥檚 new study validates findings in data collected across 10 sites, from the for Parkinson鈥檚 Progression Marker Initiative database.

鈥淭o evaluate and validate an imaging marker, it is important to confirm results across data collection sites, and the Michael J. Fox Foundation database provides a unique opportunity to do that,鈥� said lead author Roxana G. Burciu, Ph.D., a research assistant professor. The database provides a collection of clinical, imaging and biological data available for researchers to use in order to advance knowledge on Parkinson鈥檚 disease.

A key finding of the new study is that results were consistent across sites. Another important finding is that the one- and two-year increase in free-water in the posterior substantia nigra predicts long-term progression of disease symptoms.

鈥淲e found that the increase in the free-water measurement in the substantia nigra goes up every year and keeps going up over four years,鈥� Vaillancourt said.

'This means if you want to start designing studies to slow the progression of Parkinson鈥檚 disease, testing a drug on that measurement in the substantia nigra might be a good way to go. If the measurement in the substantia nigra is increasing year after year after year, and if you can stop that from occurring, you鈥檙e likely to slow or possibly stop the progression of the disease,鈥� he said.

鈥淭his has never been shown before,鈥� Vaillancourt added.

The study also found that the increase in the free-water measurement over one year鈥檚 time predicted a patient鈥檚 four-year clinical change in motor function.

鈥淚t suggests if you were able to control that measurement with medication as early as possible, then you could control long-term clinical progression,鈥� Vaillancourt said.

鈥淭his finding is a potential game changer as it could shift the way Parkinson鈥檚 disease clinical trials are designed and conducted,鈥� said , a professor and chair of neurology at the University of Florida and medical director for the Parkinson鈥檚 Foundation. 鈥淔ree-water is a validated measurement that will likely decrease the number of patients required to demonstrate the slowing of clinical progression.鈥�

The study, titled 鈥淧rogression Marker of Parkinson鈥檚 Disease: A 4-Year Multi-Site Imaging Study,鈥� was funded by the National Institutes of Health and the National Institute of Neurological Disorders and Stroke.