Understanding and identifying epigenetic changes may become a potential strategy for early Parkinson’s diagnosis, when patients still lack the characteristic symptoms of the disease, according to a recent study.
The study, “DNA methylation changes associated with Parkinson’s disease progression: outcomes from the first longitudinal genome-wide methylation analysis in blood,” was published in Epigenetics.
Parkinson’s disease patients carry a unique profile of certain epigenetic marks — modifications that sit on top of DNA and control which genes can become activated or not — that change as disease progresses.
“Using this [epigenetics] approach, you could put patients at risk for PD [Parkinson’s disease] on certain therapies before symptoms arise,” Travis Dunckley, assistant research professor at the Arizona State University’s (ASU)-Banner Neurodegenerative Disease Research Center, said in an ASU news release written by Gabrielle Hirneise.
Parkinson’s disease is characterized by the progressive loss of coordination and movement. These symptoms are currently the basis for Parkinson’s clinical diagnosis. However, they appear when the disease is in an advanced phase, a time during which current therapies are much less effective.
“One of the biggest issues with neurodegenerative diseases like Parkinson’s disease or Alzheimer’s disease is that diagnosis is mostly clinically based, and it comes late in the disease — the brain is already degenerated, and it is extremely difficult to restore brain function at that stage,” Dunckley said.
To increase the likelihood of response to available therapies, identifying the disease during its early stages — before the onset of symptoms — is key.
“When physicians treat PD [Parkinson’s disease] patients, it is usually too late to change the trajectory of the disease. I am interested in early diagnostics to try to identify people prone to the disease before they get it,” Dunckley added.
While there is a genetic component to Parkinson’s disease — estimated to contribute to 40% of disease risk — environmental factors play a key role in the disease, namely by interacting with the genome (our complete set of genes).
Parkinson’s is “about 60% environmental — it’s much less genetic than many other neurodegenerative diseases,” Dunckley said.
One way that the environment interacts with the genome is through epigenetic changes — external chemical modifications to DNA that can turn genes on or off but that do not change the actual DNA sequence.
One type of epigenetic mark is the addition of chemical methyl groups that sit on top of genes and work as “switch off” or “switch on” signals. However, unravelling the role of these epigenetic marks in Parkinson’s disease is challenging.
“It is hard to link them without confounding variables in that there are a lot of environmental factors,” Dunckley said. “It’s difficult to say whether epigenetic changes are based on disease, environmental factors or a combination of disease and environmental factors.”
Dunckley and collaborators at the University California, San Diego(UCSD), Texas A&M University, Harvard University and The Translational Genomics Research Institute (TGen), aimed to characterize the epigenetic landscape, specifically the changes in DNA methylation patterns (called methylome), over time in a group of Parkinson’s patients.
In the largest epigenetics study to date in Parkinson’s research, the scientists profiled the methylome of 189 patients and compared it to that of 191 healthy controls. After two years, the same analysis was performed to assess how the DNA methylation patterns changed in Parkinson’s patients versus controls.
The researchers found that the sites in the DNA that are methylated vary between Parkinson’s and healthy individuals, and that these methylation patterns change over time.
Patients receiving dopamine replacement therapy also had a different methylation pattern compared with untreated patients, with the patterns changing more in the untreated group — further supporting the link between epigenetic changes and Parkinson’s progression.
“The main findings are that one, the epigenome does change as the disease progresses. The second finding is that the PD medications themselves alter the epigenome,” Dunckley said.
If researchers are able to identify a methylation pattern that is specific to Parkinson’s patients, clinical diagnosis can be made earlier and allow patients to receive treatmentbefore irreversible changes occur in the brain.
The researchers are expanding these early findings by performing the same type of analysis in a new subset of patients but for longer period of time.
“The next study we are doing is a replication and extension of this one to validate the findings and extend the observation period to five years,” Dunckley said.
“We are also including patients that are very early in PD [Parkinson’s disease] progression, patients who have symptoms that are highly predictive of future PD. The ultimate goal is to identify changes in these earliest stages of disease that can be predictive of future PD onset,” he added.
https://parkinsonsnewstoday.com/2019/04/26/studying-epigenetic-changes-diagnose-earlier-parkinsons-disease-study/
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