Would you believe it if I said you can use a skin biopsy to detect a pathology of the brain? Well, that is exactly what's happening now! 2024 is full of surprises!, just last week we discussed a vaccine that can essentially cure cancer! . And now, using skin biopsy for Parkinson diagnosis has taken a step forward with the Syn-One Test. This article dives into how this test works, why it matters, and what it means for Parkinson's patients.
Latest Developments with the Syn-One Test
The Syn-One Test is a recent breakthrough in diagnosing Parkinson's disease using a skin biopsy. Developed by CND Life Sciences, it boasts a remarkable 93% accuracy rate in spotting Parkinson's. Doctors are using it across the country to help diagnose patients more accurately and quickly, although it's not FDA approved yet.
Parkinson's Disease
Parkinson's disease (PD) is a brain disorder where phosphorylated alpha-synuclein protein builds up, especially in the substantia nigra. This causes impaired protein clearance and accumulaiton due to the midfolded protein. It also causes mitochondrial dysfunction, chronic neuronal inflammation and neuronal damage. Consequently, this leads to a lack of dopamine production in substabtia nigra and resulting in PD's classical presentation - 'TRAP'.
T - Tremmor (Resting Tremmor, Pill Rolling Tremmor)
R - Rigidity (Cogwheel Rigidity)
A - Akinesia/ Bradykinesia
P - Postural Instability
S - Shuffling gait.
How Can a Skin Biopsy Detect Parkinson's?
To understand how skin biopsy can detect Parkinsons, let's look at alpha-synucleinopathies. These are diseases like Parkinson's, where a protein called alpha-synuclein builds up in the brain. Ultimately, this build up is what causes the symptoms of Parkinson's. With the Syn-One Test, doctors can now find this protein in the skin. All in all, this offers a new way to diagnose the disease.
Alpha Synuclein
The pathophysiological basis of using skin biopsy for Parkinson's disease (PD) diagnosis, lies in the aggregation of phosphorylated alpha-synuclein (P-α-Syn), a presynaptic nerve terminal protein. P-α-Syn is the primary component of Lewy bodies (LBs), proteinaceous inclusions characteristic of PD. Moreover, Familial PD often results from mutations or multiplications of the SNCA gene, which encodes α-Syn. These mutations lead to abnormal alterations in α-Syn, affecting its function and aggregation kinetics. Additionally, post-translational modifications such as phosphorylation, acetylation, nitration, and oxidation influence α-Syn aggregation and its pathological role in PD.
Skin Biopsy
In PD, α-Syn aggregates mainly in the proximal autonomic nerve fibres. So, abundant autonomic innervation makes the skin a promising site for biopsy to detect PD-related α-Syn pathology. Skin biopsy offers several advantages, including accessibility, non-invasiveness, and the ability to collect multiple samples. The deposition of α-Syn in skin. This making it a reliable method for distinguishing PD from other forms of parkinsonism. Studies have shown high sensitivity and specificity of α-Syn deposition in skin biopsies, particularly in areas innervated by spinal nerves.
To optimize the diagnostic performance of skin biopsy, careful site selection is crucial. Biopsy sites target autonomic nerve-regulated tissues where α-Syn is deposited, such as arterioles, sweat glands, and arrector pili muscles. Various techniques, including immunofluorescence staining and real-time quaking-induced conversion (RT-QuIC), have been employed to detect α-Syn aggregates in skin biopsies. These advanced methodologies offer promising avenues for establishing α-Syn assays for PD diagnosis.
Types of Skin Biopsies
| Biopsy Type | Description | Depth | Common uses |
|---|---|---|---|
| Punch Biopsy | A circular blade or punch tool is used to remove a small cylindrical core of skin tissue. | Epidermis and a portion of the dermis | Diagnosing skin conditions such as suspected skin cancers, inflammatory disorders, and infections |
| Shave Biopsy | A thin layer of skin tissue is shaved off using a scalpel or similar instrument. | Epidermis and a portion of the superficial dermis | Diagnosing superficial skin lesions, such as non-melanoma skin cancers, benign growths, and certain inflammatory conditions |
| Excisional Biopsy | A deeper and larger piece of skin tissue, along with the entire lesion or area of concern, is removed using a scalpel. | Complete removal of the lesion and extends deeper | Larger skin lesions, suspected melanomas, cases where a more extensive tissue sample is needed for diagnosis |
| Incisional Biopsy | A partial-thickness sample of the skin lesion is obtained by making an incision with a scalpel. | Cutting into the lesion but not completely | When the entire lesion cannot be safely or practically removed, such as in cases of large or deep-seated tumors |
| Punch Excision Biopsy | Combines aspects of both punch and excisional biopsies, where a larger punch tool is used to remove a deeper and wider tissue sample. | Removes a cylindrical core of tissue | Diagnosing deeper or larger lesions while still utilizing a punch technique for sample retrieval |
Research on Parkinson's and Skin Biopsy
Let's look at a few of the latest researches that have studied this test.
In the United States
In a study involving 428 participants, 92.7% of those with PD, 98.2% with MSA, 96.0% with DLB, and all individuals with PAF showed positive results in skin biopsies for phosphorylated α-synuclein. Only 3.3% of control subjects without synucleinopathy exhibited such deposits. This suggests that skin biopsy could be a sensitive diagnostic tool for synucleinopathies. However, researchers need to further validate this using broader clinical populations. This blinded, cross-sectional study, conducted across 30 sites in the US from February 2021 to March 2023, evaluated the positivity rates of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF, along with control participants without synucleinopathy.
In China
Similarly, in a separate study conducted in China, researchers explored the diagnostic utility of skin samples in detecting Parkinson's disease (PD) among the Chinese population. Particularly, this study aimed to evaluate the diagnostic performance of skin samples using Real-Time Quaking-Induced Conversion (RT-QuIC).
The study included patients clinically diagnosed with PD and controls without alpha-synucleinopathies, following stringent diagnostic criteria. Through RT-QuIC analysis of skin samples, researchers observed positive alpha-synuclein seeding activity in a significant proportion of PD patients, with high sensitivity and specificity levels. Biochemical characterization of the RT-QuIC products further confirmed the presence of fibrillary alpha-synuclein species in PD-seeded reactions, distinguishing them from control samples.
These findings highlight the potential of skin biopsy coupled with RT-QuIC technology as a reliable approach for PD diagnosis, particularly in regions with diverse populations like China. The high specificity and sensitivity demonstrated in this study underscore the feasibility of integrating skin biopsy into routine clinical practice for accurate PD detection and differential diagnosis.
Limitations
As promising as this latest development sounds, this test is not entirely specific for Parkinson disease. Rather, it gives positive result for all alpha-synucleinopathies including lewy body dementia, corticobasal degeneration, pure autonomic failure, etc. However, Parkinson's disease is the prodominant disease among all of the alpha-synucleinopathies. It accounts for approximately 70-80% of cases. Therefore, this development is most beneficial for detecting Parkinson disease. That being said, the latest research in the US has shown some promising results with it's ability to distingush PD from other alpha-synucleinopathies.
Future Prospects of Using Skin biopsy for Parkinson's
The Syn-One Test could change the game for Parkinson's patients. With earlier and more accurate diagnosis, doctors can start treatment sooner, potentially slowing down the progression of the disease. In addition, the test is affordable and easy to do, making it accessible to more people who need it.
Looking ahead, there's a lot of potential for skin biopsy in Parkinson's diagnosis. As researchers continue to study and refine this method, we may see even better ways to detect and treat Parkinson's in the future.
In conclusion, the Syn-One Test offers hope for Parkinson's patients and their families.By using skin biopsy to detect the disease early, we can improve outcomes and quality of life for those living with Parkinson's.
References
aoran Peng, Siyuan Chen, Shaopu Wu, Xiaoxue Shi, Jianjun Ma, Hongqi Yang, Xue Li,
Alpha-synuclein in skin as a high-quality biomarker for Parkinson's disease,
Journal of the Neurological Sciences, https://doi.org/10.1016/j.jns.2023.120730.
Alafuzoff I, Hartikainen P. Alpha-synucleinopathies. Handb Clin Neurol. 2017;145:339-353. doi: 10.1016/B978-0-12-802395-2.00024-9. PMID: 28987181. https://doi.org/10.1016/b978-0-12-802395-2.00024-9
Li, J., Duan, S., Yang, J. et al. Detection of skin α-synuclein using RT-QuIC as a diagnostic biomarker for Parkinson’s disease in the Chinese population. Eur J Med Res 29, 114 (2024). https://doi.org/10.1186/s40001-024-01705-x
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