Using urine and cerebral-spinal fluid samples collected from patients more than five years ago, researchers from the University of Alabama at Birmingham (UAB) have discovered a potential new way to detect, diagnose, and monitor the progression of Parkinson’s disease.
Dr. Andrew West, a professor of neurology at UAB as well as the co-director of the university’s Center for Neurodegeneration and Experimental Therapeutics, and his colleagues explained that a protein known as LRRK2 can undergo a specific type of mutation which can result in the onset of Parkinson’s, and that this biomarker can be detected in biofluids such as urine.
The most common LRRK2 mutation, identified as G2019S, causes the protein to add too many phosphates to itself and other proteins, and while doctors are not yet certain why this leads to the development of Parkinson’s, the discovery could help in the development of new drugs designed to combat the symptoms of the neurodegenerative disease, according to the research team.
“Nobody thought we’d be able to measure the activity of this huge protein called LRRK2 [pronounced ‘lark two’] in biofluids since it is usually found inside neurons in the brain,” Dr. West, whose research was supported in part by the Michael J. Fox Foundation for Parkinson’s Disease Research and the National Institutes of Health (NIH), said in a statement.
Findings could aid in the development of new treatment options
The new biomarker correlates with both the presence and severity of Parkinson’s disease, the researchers explained. Two studies detailing their findings have been published: one in March in the journal Neurology, and the second in last month’s edition of Movement Disorders.
In the March study, the researchers found that elevated levels of phosphorylated LRRK2 could predict Parkinson’s onset for the 2% to 3% of patients carrying a mutation in the protein. Those findings were evaluated in a preliminary, 14-person cohort of stored urine samples which was followed by a larger replication study of 72 biobanked specimens.
In the second study, Dr. West and his colleagues expanded their analysis to Parkinson’s patients who did not have the LRRK2 mutations. Using 158 urine samples from both Parkinson’s patients and healthy control subjects, they found that roughly one-fifth of people who lacked the LRRK2 mutations but who had the neurodegenerative condition also had highly elevated phosphorylated LRRK2 similar to those with the mutations – a trait not found in control subjects.
The results suggest that people with elevated phosphorylated LRRK2 may be particularly good candidates for future drugs that reduce phosphorylated LRRK2, and the authors of those papers are hopeful that their findings will help pave the way for an inhibitor that has already proven to be successful at preventing neuroinflammation and neurodegeneration in animal models.
“New biochemical markers like the one we’ve discovered together with new neuroimaging approaches are going to be the key to successfully stopping Parkinson’s disease in its tracks,” said Dr. West. “I think the days of blindly testing new therapies for complex diseases like Parkinson’s without having active feedback both for ‘on-target’ drug effects and for effectiveness in patients are thankfully coming to an end.”
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Image credit: UAB News
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