Can this first-of-its-kind guideline for identifying biomarkers in Parkinson disease invigorate a drive for disease-modifying therapy development?
Alice S. Chen-Plotkin, MD, the Parker Family Associate Professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania
A new slate of guidelines has been published to inform research into the identification of biomarkers in Parkinson disease—the first to be developed in collaboration with institutions outside of medical academia, including the Michael J. Fox Foundation for Parkinson Research.1
"These players at times have acted in separate worlds, but with a disease affecting so many and lacking in disease-modifying therapies, we're coming together for essential collaboration and innovation," Alice S. Chen-Plotkin, MD, the Parker Family Associate Professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania said in a statment.2 "Biomarkers to bolster our efforts to develop new therapies are urgently needed. These guidelines can help make the discovery of biomarkers for Parkinson's a reality."
Currently, more than 500 studies are listed as ongoing in Parkinson disease, but only about 10% of those are assessing a disease-modifying or neuroprotective therapy. Why is the pipeline for these essential therapies facing a drought despite the disease’s prevalence?
While previous trials of these kinds of therapies have failed, for this group of researchers, the answer to this problem lies in the identification process, with biomarkers. They stressed that finding biomarkers in the near future could have a great, immediate impact on the development of disease-modifying therapies in Parkinson disease.
The guidelines focus on a trio of recommendations for the types of biomarkers that would be the most useful for the development of therapies. Most notably, the authors argue a shift from the emphasis of previous guidelines, away from biomarkers which help distinguish the condition from other neurodegenerative conditions or healthy individuals and toward those that identify the different manifestations of Parkinson itself.
“We argue that PD biomarkers that are likely to be useful in a clinical trial context should be of reasonable effect size alone or in combination (for example, demonstrate an area under the curve of >0.8) and robust, by which we mean that they must demonstrate clear reproducibility across patient cohorts,” Chen-Plotkin and colleagues wrote. “Notably, it would be preferable if the biomarker could be verified in neuropathologically proven cases of PD, given recent studies indicating that only two out of three patients seen at a first visit and given a diagnosis of possible or probable PD have PD on autopsy. Finally, practical considerations, such as cost and complexity of assays to detect biomarkers and the capability for frequent or serial testing, need to be considered early in PD biomarker discovery and development.”
The team of researchers pointed toward shared biobanks that have been built at centers around the world, which hold thousands of blood and tissue samples, as a possible starting point. These biobanks, the investigators argue, could hold the clues to push to the next breakthrough in biomarkers.
“Before the advent of these shared biobanks, investigators depended on their own ability to collect hundreds or thousands of samples for testing, preventing potential researchers lacking access to large clinical populations from entering the biomarker discovery arena,” Chen-Plotkin explained. “However, within the last 5 years, multiple public-private efforts have laid the groundwork for investigators from both academic and industrial sectors to access well-documented clinical samples. These repositories are all open for collaboration to improve the pipeline to take Parkinson’s biomarkers from concept to clinic.”
The full guidelines can be accessed here.
1. Chen-Plotkin AS, Albin R, Alcalay R, et al. Finding useful biomarkers for Parkinson’s disease. Sci Tansl Med. 2018;10(454): eaam6003.
2. First-of-its-Kind Parkinson’s Disease Biomarker Guidelines Invigorates Drive for Treatments [press release]. Philadelphia, PA: Penn Medicine; August 15, 2018. pennmedicine.org/news/news-releases/2018/august/first-of-its-kind-parkinsons-disease-biomarker-guidelines-invigorates-drive-for-treatments. Accessed August 23, 2018.