Sunday, Jan 29, 2023

A novel test may help in early diagnosis of Parkinson’s

A team from IIT-B, led by Prof Samir Maji, has developed a technology that can measure toxic protein aggregates

parkinson's diagnosisOne of the most potent causes of PD is a special form of toxic protein aggregates (amyloids) formed by alpha-synuclein, which kills neuronal cells in the brain (Source: Getty Images/Thinkstock)
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A novel test may help in early diagnosis of Parkinson’s
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It is now a well-known fact that early diagnosis of Parkinson’s Disease (PD) can help a patient reduce the risk of progression and live long and productively enough with this neuro-degenerative condition. It is this quest for detecting early signs that drove researchers at the Indian Institute of Technology-Bombay (IIT-B) to develop a blood-based assay. And now they have achieved a 95 per cent accuracy in detecting the disease early enough in a small cohort of patients at the KEM Hospital.

One of the most potent causes of PD is a special form of toxic protein aggregates (amyloids) formed 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. The researchers from IIT-B’s Department of Biosciences and Bioengineering, led by Prof Samir Maji, have developed a technology that entails a substrate added to blood samples. This amplifies the protein aggregates if present. As the aggregates amplify, they can be easily measured and confirm PD.

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

“The deposition of plaques (aggregates) of proteins in the brain is one of the pathological characteristics of many neuro-degenerative disorders, including PD. Alpha-synuclein, a presynaptic protein, is thought to play a major role in vesicular trafficking and neurotransmitter release. However, aberrant misfolding and accumulation of this protein have been directly correlated with the pathogenesis of PD. 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 the neuronal cells in the specific brain regions, which control muscle tone, movement regulation and cognitive function,” explains Prof Maji.

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Right now, the standard diagnosis for Parkinson’s is clinical; there is no test. So developing a conclusive test for Parkinson’s is still very challenging. Says Prof Maji, “Till date, the detection of Parkinson’s Disease is solely based on the characteristic symptoms of the disease (tremors, rigidity, motor dysfunction, cognition disorders, etc.). However, by the time the symptoms arise, 70 per cent of the dopaminergic cells in the brain have already died and the level of dopamine is drastically reduced. Studies carried out so far have remained unsuccessful in devising effective diagnostics for detecting the disease at earlier stages due to the absence of detectable physical symptoms (before the appearance of large-scale neurodegeneration), specific biomarkers (representing the disease initiation), and overlapping symptoms with ageing 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. Regular brain imaging techniques, such as MRI, PET scans might not be sensitive enough to map such small changes in the brain and distinguish them from other neuro-degenerative diseases and ageing. Thus, there is an unmet need to identify biomarkers that can detect the disease in the early stages.”

“We have developed a novel substrate to amplify these ultra-low quantities 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 assay but a large-scale clinical trial is required to determine its sensitivity and specificity. “At present, the method of amplifying the small quantities of alpha-synuclein aggregates in the blood is highly time-consuming but with time, we might come up with solutions so that we can detect them in less time in a less expensive way,” says Prof Maji.

First published on: 22-01-2023 at 06:00 IST
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