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A New Visual Diagnosis Protocol for Neurodegenerative Diseases

Digital illustration of human brain with orange marking

Neurodegenerative diseases like amyotrophic lateral sclerosis, multiple sclerosis, and Parkinson’s disease all have devastating impacts, significantly reducing patients’ quality of life as the disease progresses. Thus, early detection and treatment are key. However, many of these diseases present significant barriers to early detection. Parkinson’s disease is no exception.

Though it affects millions worldwide, Parkinson’s disease is relatively difficult to diagnose in its earliest stages, even in a sophisticated clinical setting. Fortunately, researchers at the University of Minnesota have developed a new visual diagnostic technique that can be used in the early detection of neurodegenerative diseases. The research, entitled “Visual detection of misfolded alpha-synuclein and prions via capillary-based quaking-induced conversion assay (Cap-QuIC),” was recently published in npj Biosensing. Its protocol could significantly impact neurological testing standards.

Barriers to Early Diagnosis for Neurodegenerative Diseases

Unfortunately, many diagnoses of Parkinson’s disease derive from external symptoms observed in clinical settings. These symptoms include cognitive decline, motor fluctuations, and recurrent falls. By the time patients develop these noticeable symptoms, they are often already in the advanced stages of the disease, which limits their therapeutic options. Therefore, early detection methods are highly sought after.

Early detection of neurodegenerative diseases generally requires expensive, highly sophisticated equipment, which is out of reach for many patients and care providers. But now, the aforementioned University of Minnesota researchers have identified a visual method for potential early detection. The method focuses on the surface characteristics of malformed alpha-synuclein proteins in the brain, which can be indicative of a diseased state. With the new protocol, these proteins can be observed visually without the use of costly, inaccessible equipment. This could improve early disease detection, particularly in remote or under-resourced areas without access to precision testing equipment.

Visual Analysis of Neurodegenerative Disease Markers

To observe differences between normal and disease-associated alpha-synuclein proteins, the team used glass capillaries, which are small test tubes designed to hold biological materials in clinical settings. By placing the proteins within the tubes surrounded by a neutral liquid, the researchers were able to observe differences in liquid movement; such differences are caused by modifications in protein surface characteristics. In the capillaries, the surface of liquid containing misfolded protein showed a less concave meniscus than liquid containing native protein. Essentially, the diseased proteins moved in a notably different way when compared to normal proteins. The researchers dubbed the protocol Cap-QuIC (Capillary-enhanced Quaking-Induced Conversion).

The researchers tested the technique on tissues from wild white-tailed deer infected with Chronic Wasting Disease, which is a neurodegenerative disease impacting deer. Ultimately, the team showed that Cap-QuIC could classify samples with a high degree of reliability. “Our Cap-QuIC procedure represents a major advancement in point-of-care neurodegenerative disease diagnostics,” said Professor Sang-Hyun Oh, senior co-author of the paper. “By simplifying the detection process, we can potentially diagnose Parkinson’s disease earlier, which is crucial for effective management and treatment.”

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Using this new method, researchers will now be able to distinguish infected samples with the naked eye, which makes testing more accessible and cost-effective. This builds upon the researchers’ previous diagnostic technique, which allowed for faster and more accurate disease detection during routine screenings. With techniques like this one, screening for neurodegenerative diseases like Parkinson’s disease will be faster, more affordable, and more accessible for patients all over the world. That level of improved detection can help ensure an improved quality of life for patients with Parkinson’s disease, as well as their caretakers.

At Scantox Neuro, several preclinical models facilitating alpha-synuclein research are available that allow researchers to evaluate the effect of new treatments on alpha-synuclein pathology in vitro and in vivo. Models of alpha-synuclein aggregation, seeding and autophagy allow to analyze the efficacy of experimental drugs in vitro. Available in vivo models include different D-Line, Line 61, and hA53Tg transgenic mice as well as AAV2 hA53T-α-syn induced mice. Behavioral tests in rodents enable the analysis of the Parkinson’s disease phenotype. Scantox has established further molecular and histological evaluations of the Parkinson’s pathology for ex vivo tissue analysis, and tissue of Parkinson’s animal models is readily available in our Biobank.

Scantox is the leading Nordic preclinical GLP-accredited contract research organization (CRO), delivering the highest grade of pharmacology and regulatory toxicology services since 1977. Scantox focuses on preclinical contract research services, supporting pharmaceutical and biotechnology companies with their drug development projects. Core competencies include explorative and efficacy studies, PK studies, general toxicology studies, local tolerance studies, wound healing studies, and vaccines. For more information about Scantox, visit https://scantox.com.