Rapid Blood Test Identifies Pre-Symptomatic Patients with Parkinson’s Disease

Currently, no reliable blood test exists for diagnosing Parkinson’s disease. Instead, physicians rely on observing a patient's movements, but this qualitative method has an error rate of 20%-25% and can only be used after the disease has advanced and significant symptoms are present. Another test, involving a spinal tap, cannot track disease progression and is costly and uncomfortable for patients. Now, researchers have developed a new diagnostic test that measures transfer RNA fragments (tRFs) from nucleated red blood cells to identify pre-symptomatic Parkinson’s patients and monitor disease progression.

Researchers at Hebrew University (Jerusalem, Israel) in collaboration with ATED Therapeutics (Greenwich, CT, USA), have developed a simple, reliable, and cost-effective blood test that could revolutionize Parkinson’s diagnosis. This test can accurately identify whether someone is developing Parkinson’s before symptoms even appear. The researchers took a novel approach by analyzing tRFs, which had previously been overlooked in Parkinson’s research, to detect the disease at its earliest stages. Their study revealed a recurring pattern of tRNA fragments in the cerebrospinal fluid of Parkinson’s patients. The researchers identified two key biomarkers with altered patterns, potentially indicating significant biological changes linked to neurodegeneration.

First, they discovered tiny tRFs with a specific pattern based on seven building blocks of RNA and DNA. These tRFs were named RGTTCRA fragments, after the RNA molecules involved in the pattern. They also identified another set of fragments originating from mitochondria, the energy-producing components of cells, which are known to be damaged in Parkinson’s disease. Parkinson’s patients had higher levels of RGTTCRA-tRFs and lower levels of mitochondrial tRFs compared to healthy individuals. By measuring the ratio of these biomarkers, the test can differentiate pre-symptomatic Parkinson’s patients from healthy individuals. The test uses the same lab technique employed in COVID-19 diagnostics, measuring the amounts of each RNA fragment in a blood sample and calculating their ratio.

To validate their discovery, the researchers tested blood samples from 60 Parkinson’s patients and 60 healthy controls. The patients, who were experiencing early symptoms such as loss of smell and difficulty sleeping, had not yet developed the hallmark symptoms like tremors. The researchers analyzed the ratio between RGTTCRA-tRFs and mitochondrial tRFs and used machine learning to predict which participants were pre-symptomatic Parkinson’s patients and which were healthy. Published in the journal Nature Aging, the results showed that the blood test correctly identified the disease in about 86% of cases, outperforming current diagnostic methods. Furthermore, the test can also measure the effects of deep brain stimulation (DBS), a common treatment for Parkinson’s. The researchers are currently in talks with pharmaceutical companies to conduct the test on a larger and more diverse cohort, a necessary step for FDA approval.