New test may aid in early diagnosis of Parkinson’s

It is now recognized that early diagnosis of Parkinson’s disease (PD) can help a patient reduce the risk of progression and live long and productively with this neurodegenerative condition. It is this quest to detect early signs that prompted researchers at the Indian Institute of Technology-Bombay (IIT-B) to develop a blood-based test. And now they have achieved 95% accuracy in detecting the disease fairly early in a small cohort of patients at KEM hospital.

One of the most potent causes of Parkinson’s disease is a special form of toxic protein aggregates (amyloids) formed from alpha-synuclein, which kills neuronal cells in the brain. These alpha-synuclein protein aggregates also cross the blood-brain barrier and enter the bloodstream in small quantities. Researchers from the IIT-B Department of Biosciences and Bioengineering, led by Prof Samir Maji, have developed a technology that involves adding a substrate to blood samples. This amplifies the protein aggregates if present. As the aggregates amplify, they can be easily measured and confirm PD.

After achieving 95% success in early diagnosis, the department is conducting large-scale, high-throughput clinical trials for the patented technology.

“The deposition of protein plaques (aggregates) in the brain is one of the pathological features of many neurodegenerative disorders, including Parkinson’s disease. Alpha-synuclein, a presynaptic protein, is thought to play an important role in vesicular trafficking and neurotransmitter release. However, the aberrant misfolding and accumulation of this protein has been directly related to the pathogenesis of Parkinson’s disease. For example, the natively unstructured protein undergoes a structural transition into higher-order fibrillar aggregates. Lewy bodies and Lewy neurites are the deposits of these aggregated proteins found in neuronal cells in specific brain regions, which control muscle tone, movement regulation and cognitive function,” explains Prof. Maji.

At this time, the standard diagnosis for Parkinson’s is clinical; there is no proof. So developing a conclusive test for Parkinson’s is still very challenging. Says Prof. Maji: “To date, the detection of Parkinson’s disease is based solely on the characteristic symptoms of the disease (tremors, rigidity, motor dysfunction, cognitive impairment, etc.). However, by the time symptoms do arise, 70% of the dopaminergic cells in the brain have already died and the level of dopamine is drastically reduced. Studies to date have been unsuccessful in devising effective diagnostics to detect the disease in earlier stages due to the absence of detectable physical symptoms (before the onset of large-scale neurodegeneration), specific biomarkers (representing the onset of disease) and overlapping symptoms with aging and other neurodegenerative disorders. Furthermore, the initial loss of specific dopaminergic neurons in the Substantia Nigra pars Compacta (SNc) region of the brain is a very small change. Standard brain imaging techniques, such as MRIs and PET scans, may not be sensitive enough to map such small changes in the brain and distinguish them from other neurodegenerative diseases and aging. Therefore, there is an unmet need to identify biomarkers that can detect the disease in its early stages.”

“We have developed a novel substrate to amplify these extremely low amounts of aggregated alpha-synuclein species, which may be specific to Parkinson’s disease patients,” he adds. A small group has validated this test, but a large-scale clinical study is needed to determine its sensitivity and specificity. “Currently, the method to amplify the small amounts of alpha-synuclein aggregates in the blood is time-consuming, but over time we may find solutions so that we can detect them in less time and in a less expensive way.” says Prof Maji.

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