The Michael J Fox Foundation has announced the findings of a landmark paper that identified a biomarker for Parkinson’s disease with high accuracy, which may be able to indicate disease before typical symptoms appear. The researchers believe the biomarker will allow scientists to finally define Parkinson’s disease biologically, opening up new routes in diagnostics and potential therapies.
Written by the leaders of the Parkinson's Progression Markers Initiative (PPMI), a long-term investigation into the biological basis of Parkinson’s disease, the paper outlines how the new test could be used for early diagnosis and to identify exact molecular subtypes, leading to optimal treatment.
"Validation of this biomarker launches a new, biological era in Parkinson's research," said Dr Kenneth Marek, PPMI Principal Investigator and president and senior scientist at the Institute for Neurodegenerative Disorders, in a statement.
"Using αSyn-SAA, we are already unlocking new understanding of Parkinson's, which will transform every aspect of drug development and ultimately clinical care. We will rapidly be in a position to test new therapies in the right populations, target the right therapy to the right patient at the right time, and launch studies of agents with potential to prevent Parkinson's disease altogether. This is what PPMI was built to do, and we are especially grateful to the thousands of study participants whose contributions have enabled this watershed moment."
The new test looking for the specific biomarker is called the alpha-synuclein seed amplification assay (αSyn-SAA) and looks for synuclein pathology. Alpha-synuclein is a protein found in neurons, which, in some people, begins to misfold as it forms, creating clumps of damaged proteins called Lewy bodies. While researchers are still unclear whether Lewy bodies cause Parkinson’s, they are one of the clearest hallmarks of the disease that scientists have.
The test was developed as part of the PPMI and used patients enrolled in the initiative to validate it, the results of which are outlined in the team’s paper. Taking 1,100 people from PPMI, the team used αSyn-SAA on a variety of people, including those with prior risk factors, people with and without risk genes, and more.
They found that the test was around 90 percent accurate on people with typical Parkinson’s pathology, a figure which raised even more in people with smell loss and sporadic Parkinson's without a known causal genetic mutation. In people that had not been diagnosed with Parkinson’s, the assay was positive around 90 percent of the time if they had a loss of smell or REM sleep behavior disorder, both of which are linked with the disease.
The assay was able to detect synuclein pathology prior to DAT imaging seeing dopamine loss, which is currently one of the earliest screenings possible for Parkinson’s. Using the assay in conjunction with other tests may extend the window in which researchers can introduce preventative measures.
While the assay seems to be extremely accurate, it remains unclear how successful it will be in identifying Parkinson’s prior to any symptoms. This study found it to significantly drop in effectiveness when people had no olfactory deficit and an even larger drop when they had a certain genetic variant, so it may not be particularly reliable as a standalone indicator.
The team are now building a longitudinal cohort of around 2,000 people with no diagnosis of Parkinson’s to validate the test against, but such studies take time and require a lot of resources. Still, if anyone can do it, it will be the PPMI.
"There are many ways I am involved with the work of the Foundation, but I come to this result first and foremost as a Parkinson's patient. I am deeply moved by this breakthrough and endlessly grateful to the researchers, study participants and funders who have endeavored to bring us this far,” said Michael J Fox.
“When we started PPMI, we weren't casting about for fish – we were going after a whale. Now, here we are. Together we are making a cure for Parkinson's inevitable."
The study is published in The Lancet Neurology.