Using Cutaneous Synuclein Biosignatures to Distinguish Parkinson’s Disease From Multiple System Atrophy
A recent paper published in Neurology and co-authored by two of CND Life Sciences’ co-founders, Christopher Gibbons and Roy Freeman (and other academic colleagues), presented the first-ever data suggesting the possibility that measurable pathological markers in the skin can reveal distinct biological characteristics to help separate one type of synucleinopathy from another.
Applying the core scientific methods used by CND’s Syn-One Test®, the authors discuss the concept of cutaneous pathological signatures that help discriminate between the phenotypically and biochemically similar neurodegenerative disorders Parkinson’s disease and multiple system atrophy (MSA). The authors, in effect, introduce an exciting potential tool that could be used in clinical practice to aid a physician’s diagnosis and treatment pathway for specific patients and could be incorporated into biopharmaceutical clinical trials.
Entitled “Cutaneous α-Synuclein Signatures in Patients With Multiple System Atrophy and Parkinson Disease,” the paper offers a unique and important window into the underlying pathology of two diseases, which are difficult to distinguish early in their course and have very different prognoses. A hallmark of both disorders is the presence of phosphorylated alpha-synuclein in the central nervous system, which at autopsy can be seen as structures called Lewy bodies or Lewy neurites. Gibbons et al sought to discover if these Lewy neurite-like deposits, visualized using simple punch biopsies of the skin, could be used to distinguish between Parkinson’s and MSA.
The study examined 31 patients with MSA and 54 patients with Parkinson’s as well as 24 matched controls. All participants underwent neurologic examinations, autonomic testing, and skin biopsies at three locations. The density of intraepidermal, sudomotor, and pilomotor nerve fibers was measured. The deposition of phosphorylated alpha-synuclein was quantified and examined topographically.
All patients with MSA and 51/54 with Parkinson’s had evidence of phosphorylated alpha-synuclein in at least one skin biopsy. No phosphorylated alpha-synuclein was detected in controls. Patients with MSA had greater phosphorylated alpha-synuclein deposition (P<0.0001) and more widespread peripheral distribution (P<0.0001) than patients with Parkinson’s. The study also found that patients with Parkinson’s had reduced nerve fiber densities compared to patients with MSA (P<0.05, all fiber types). The combination of quantitative phosphorylated alpha-synuclein deposition with the relative distribution of phosphorylated alpha-synuclein provided >90% sensitivity and specificity in distinguishing between the two disorders. The authors thus describe this finding as a specific biosignature that can distinguish Parkinson’s from MSA.
If validated in larger prospective studies, the cutaneous synuclein biosignature would be the first clinically available technology to accurately distinguish Parkinson’s disease from MSA and could become a standard, supplemental offering with the Syn-One Test.
