An exciting development is underway as a new RNA-based blood test could help diagnose Parkinson’s disease (PD) prior to the development of motor symptoms. The work, published in Nature Aging, demonstrated a way to target and detect specific sequences contained within transfer RNA (tRNA) for early diagnosis in a simple blood test. This approach will hopefully continue to be developed into a commercially available laboratory test, making it the first blood-based test to help diagnose PD.
How the Blood Test Works
While the test itself is relatively quick and easy to run, the science behind its development is extensive. The key element to the test is a fragment of tRNA— a type of RNA molecule traditionally known for its role in protein synthesis and often an overlooked piece in diagnostic tools. Recently, it has been found that tRNA can be cleaved into fragments that play various regulatory roles in cells, including adaptations to cellular stress that may be particular to a specific disease state such as PD.
In this blood test, the researchers focused on quantifying specific short, repetitive sequences within these tRNA fragments called motifs. These motifs were utilized as biomarkers to compare PD patients to healthy controls in order to determine differences that may be targetable by the test.
Two biomarkers were identified within this study to pursue their validity in this early diagnostic test. By comparing known PD patient blood samples to healthy controls, a nuclear-derived tRNA biomarker was found to be elevated in PD patients (a PD specific tRNA fragment), while a mitochondrial tRNA biomarker was found to be reduced in the same PD-affected tissue (indicative of a further progression of the disease).
The analysis of the ratio in these two biomarkers was capable of distinguishing between late-stage symptomatic PD patients, patients at risk (pre-symptomatic), and healthy individuals. In fact, when moved into a large cohort of individuals, the test was found to have an accuracy of 86%.
“This discovery represents a major advancement in our understanding of Parkinson’s disease and offers a simple, minimally-invasive blood test as a tool for early diagnosis,” said Prof. Hermona Soreq, Research Advisor on the publication and neurologist at the Hebrew University of Jerusalem. “By focusing on transfer RNA fragments, we’ve opened a new window into the molecular changes that occur in the earliest stages of the disease.”
Why is This a Major Progression in the Field?
Currently, PD is typically diagnosed in the clinic with a neurological exam, based on the presence of motor symptoms. The tRNA fragment blood test offers a cheap, fast, and minimally invasive method to potentially catch the disease before motor symptoms develop, allowing for earlier diagnosis. It could be offered to those with pre-motor PD symptoms such as REM behavior sleep disorder or smell loss, or to those with a family history or known genetic mutation that increases the risk of PD.
If ultimately approved by the FDA for use, the tRNA blood test would join other lab and imaging based diagnostic tests for PD that have become commercially available in recent years and are currently being studied to determine their usefulness in diagnosing PD before motor symptoms begin.
Many other blood-based diagnostic PD tests are in research stages as well, including efforts funded by APDA.
An FDA Approval
This Parkinson’s test is a part of a larger wave of innovation for minimally invasive diagnostics. These blood-based tests are being used in a variety of diseases including cancer and other neurological disorders.
A major breakthrough in this space occurred when the FDA recently approved a blood test for Alzheimer’s disease (AD) that detects an AD-specific biomarker called amyloid plaques. This test has been approved for individuals over the age of 55 exhibiting the symptoms of Alzheimer’s disease.
This FDA approval sets a precedent that could benefit the Parkinson’s blood test. Regulatory agencies may now be more open to fast-tracking similar diagnostics, especially if they demonstrate strong predictive power, safety, and clinical utility. Early detection tools for AD and PD could even be integrated into a single screening panel in the future.
Where Do We Go from Here?
The tRNA fragment blood test will undergo further testing before its widespread use in the clinic. Next steps will include validating the test in larger and more diverse populations, including patients with atypical Parkinsonian syndromes or overlapping neurodegenerative diseases.
The test could even be expanded to evaluate additional predictive biomarkers to improve its accuracy and reduce false positives. A step further would be to combine the blood test with genetic screening and neuroimaging data to further enhance its capabilities. Clinical trials could also adapt the test for monitoring disease progression or assessing the effectiveness of treatment. Since tRNA fragments reflect dynamic changes in cellular health, they could be useful not just for diagnosis, but also for tracking how a patient responds to a new neuroprotective drug or lifestyle intervention.
If further studies confirm its accuracy and utility, this technology could even become a routine part of neurological health assessments. At the very least, it provides evidence that tRNA fragments once mostly overlooked may be a vital component in future diagnostic tools for PD and beyond.
As always, APDA remains committed to bringing you the latest news and updates. We will share further information about this blood test as it becomes available.