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Home » ‘Soft’ Symptoms Detected Before Parkinson’s Disease
Disease Discoveries

‘Soft’ Symptoms Detected Before Parkinson’s Disease

By Will DossJan 15, 2020
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Tanya Simuni, MD, chief of Movement Disorders in the Ken and Ruth Davee Department of Neurology and the Arthur C. Nielsen, Jr., Research Professor of Parkinson’s Disease and Movement Disorders, was the lead author of a study published in Lancet Neurology.

People who carry genetic mutations associated with an increased risk for Parkinson’s disease may exhibit minor symptoms long before the disease progresses to affect daily life, according to a Northwestern Medicine study of over 300 patients published in Lancet Neurology.

These subtle motor impairments could inform a diagnostic tool in the future, according to Tanya Simuni, MD, chief of Movement Disorders in the Ken and Ruth Davee Department of Neurology and lead author of the study. 

“Among those who carry risk mutations, only a minority will ultimately develop Parkinson’s disease,” said Simuni, who is also the Arthur C. Nielsen, Jr., Research Professor of Parkinson’s Disease and Movement Disorders. “There is a lot of interest in tools that can determine who has the highest risk of developing Parkinson’s, and this is the first step in asking that question.”

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that can cause loss of muscle control, trembling, stiffness and impaired balance. As the disease progresses, it can become difficult to walk, talk and complete simple tasks.

While there are treatments that can mitigate some of these symptoms, there is no therapy that can prevent or delay progression of the disease. The current diagnosis is based on clinical features — largely the motor function deficits — and the underlying disease pathology has already been progressing for years by the time these symptoms manifest, according to Simuni. 

“When someone comes into the clinic with the earliest physical motor signs of the disease, there already is about a 50 percent loss of relevant brain cells,” Simuni said. 

To investigate what’s called the pre-motor phase — the period of time during which brain cells are dysfunctional but before motor symptoms begin — Simuni and other scientists in the Parkinson’s Progression Markers Initiative (PPMI) examined about 300 participants with inherited genetic mutations that predispose them to PD, comparing them to normal healthy controls. 

The scientists found that a subset of participants with PD-associated mutations exhibited a series of “soft” clinical features, including increased scores on tests measuring muscle stiffness or slowness of movement. 

“These features were certainly not enough to make a diagnosis of Parkinson’s, but they do look different than healthy controls,” Simuini said. 

Participants also underwent dopamine transporter scans to measure the level of brain dopamine, a neurotransmitter that drives Parkinson’s motor symptoms. Unexpectedly, levels of dopamine were higher, not lower, in carriers of genetic mutations. the levels were higher and not lower in the carriers of genetic mutations. 

“That indicates that potentially the brain of at risk individuals tries to compensate prior to development of the disease providing a window of opportunity,” Simuni said.

The late diagnosis of PD complicates potential treatments: scientists are unable to test therapies on early-stage PD patients if they can’t identify these patients to begin with, and starting treatment so late into the disease would blunt its curative effects. 

Sorting people with PD-associated genes into stratified risk categories could help scientists identify early warning signs that could aid in developing both a diagnosis and treatment, according to Simuni. 

As the PPMI continues, Simuni and other scientists will continue to follow these participants and collect longitudinal data, hopefully informing a clinical tool that can be used to identify people at high risk of PD beyond just the presence of mutations.

This study was supported by the Michael J Fox Foundation for Parkinson’s Research. 

Genetics Neurology and Neuroscience Research Women in Medicine
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