Understanding Parkinson’s Requires a Change in Approach, Experts Say

Understanding Parkinson’s Requires a Change in Approach, Experts Say
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Increasing treatment success in Parkinson’s requires a change in the way researchers and doctors view and approach this disease, experts wrote in two recent studies.

“The time has come to ask what we should be doing differently,” Alberto Espay, MD, senior author of both studies, said in a news release. “Medical science has made a global investment of $23 billion in therapies with the promise to slow down the progression of Parkinson’s disease, and the 17 completed phase III clinical trials have yielded little more than disappointment.

“We need to ask whether the growing number of failed trials might be explained by our single-target and single-disease approach to drug development,” he said.

In the study, “Precision Medicine For Disease Modification In Parkinson Disease,” published in the journal Nature Reviews Neurology, researchers explain that Parkinson’s disease is a complex condition that includes different clinical, epidemiological and genetic subtypes, and it is not a “single” disease.

“Approaching [Parkinson’s disease] as a single diagnostic entity has been effective for developing symptomatic therapies but ineffective when targeting neuroprotection or attempting disease modification,” researchers wrote. “The growing number of failed attempts to establish neuroprotective therapies for [Parkinson’s disease] might in part be explained by a simplistic single-target approach to drug development.”

The authors argue that treatment and management of Parkinson’s disease should take into account the specific symptoms and differences of each patient. Indeed, patients should be classified into different clusters according to their similarities in terms of genetic and clinical manifestations and treated accordingly. They also said that the search for biomarkers should be based on these patient clusters for a better definition of Parkinson’s disease patterns, and not in different patient populations that frequently hide disease particularities.

“Looking at the disease from a systems biology perspective allows us to recognize that our patients can be divided into subtypes based on genetic, biological and molecular abnormalities,” Espay said. “As a result, they will respond differently to different therapies.”

In the second study, “Biomarker-Driven Phenotyping In Parkinson’s Disease: A Translational Missing Link In Disease-Modifying Clinical Trials,” published in the journal Movement Disorders, researchers call for a change in the search and use of Parkinson’s disease biomarkers.

Current therapies are based on the identification of biomarkers associated with symptoms that predict whether initial disease stages will lead to Parkinson’s, but the researchers’ view is that this method is much too general to include all patients and increase success rates.

“We suggest, instead, that subtyping [Parkinson’s disease] requires the reverse view, where abnormal biological signals (i.e., biomarkers), rather than clinical definitions, are used to define disease [subtypes],” they wrote. “This precision-medicine approach will likely yield smaller, but well-defined, subsets of [Parkinson’s disease] amenable to successful neuroprotection.”

“The diagnosis of Parkinson’s disease will be complete only when a biomarker profiling is capable of identifying the molecular subtypes of disease and suggest a disease-modifying treatment to apply,” Espay said.

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