A new test could help in the early diagnosis of Parkinson’s disease

It is now a well-known fact that early diagnosis of Parkinson’s disease (PD) can help the patient reduce the risk of progression and live long enough and productively with this neurodegenerative condition. It was this quest to detect early signs that drove researchers at the Indian Institute of Technology Bombay (IIT-B) to develop a blood-based test. And now they have achieved 95 percent accuracy in detecting the disease early enough in a small group of patients at KEM Hospital.

One of the strongest causes of PD is a special form of toxic protein clumps (amyloid) created by 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 amounts. Researchers from the Department of Biosciences and Bioengineering of IIT-B, led by Prof. Samir Maji, they developed a technology that involves adding a substrate to blood samples. This enhances protein aggregates if present. As aggregates are amplified, PD can be easily measured and confirmed.

Having achieved a 95 percent success rate in early detection, the department is in the process of conducting large-scale, high-throughput clinical trials for the patented technology.

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

Currently, the standard diagnosis for Parkinson’s disease is clinical; there is no test. Therefore, developing a definitive test for Parkinson’s disease is still very challenging. Prof. Maji says: “To date, the detection of Parkinson’s disease is based solely on the characteristic symptoms of the disease (tremors, stiffness, motor dysfunction, cognitive disorders, etc.). However, by the time symptoms appear, 70 percent of the dopaminergic cells in the brain have already died and dopamine levels are drastically reduced. Studies that have been carried out so far have been unsuccessful in designing effective diagnostics to detect the disease in earlier stages due to the absence of visible physical symptoms (before the onset of large-scale neurodegeneration), specific biomarkers (representing the onset of the disease) and symptoms that overlap with aging and other neurodegenerative disorders. . Moreover, the initial loss of specific dopaminergic neurons in the Substantia Nigra pars Compacta (SNc) region of the brain is a very small change. Common brain imaging techniques such as MRI, PET scan 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 new substrate to amplify these ultra-low amounts of aggregated species of alpha-synuclein, which could be specific to patients suffering from Parkinson’s disease,” he adds. A small cohort has validated this test, but a large clinical trial is needed to determine its sensitivity and specificity. “Currently, the method of amplifying small amounts of alpha-synuclein aggregates in the blood is very time-consuming, but over time we could find a solution to detect them in a shorter time and in a cheaper way,” says Prof. Maji.

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