Skin Test Detects Neurodegeneration Risk in 75% of iRBD Cases, With Todd Levine, MD

In a study presented at SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies, on Monday, June 9 in Seattle, 75% cases of REM sleep behavior disorder (RBD) at the initial visit had detected phosphorylated alpha-synuclein (P-SYN).1,2

At the meeting, HCPLive spoke with investigator Todd Levine, MD, from CND Life Sciences, on the significance of these findings, how the Syn-One Test works, and how skin biopsy-based tests may change the diagnostic workflow for patients presenting with suspected idiopathic RBD (iRBD).

“Looking at those very early patients, we were able to detect this pathological protein in 75% of the patients,” Levine said. “[This] indicates that about 3 in 4 patients with REM behavior disorder are at risk for developing these neurodegenerative diseases, and that we can detect that protein as early as 10 or maybe even 15 years before the neurodegenerative disease starts.”

iRBD, a sleep disorder that causes individuals to act out their dreams through violent movements and vocalizations, is an early indicator for future neurodegenerative conditions involving P-SYN, such as Parkinson Disease, dementia with Lewy bodies, and multiple system atrophy. A previous study showed that 73.5% of patients diagnosed with iRBD had Parkinson Disease, dementia with Lewy bodies, or multiple system atrophy within 12 years.

Using the Syn-One Test, Levine and colleagues assessed the presence of P-SYN in skin biopsies in 76 patients with iRBD (30% females; mean age, 67.8 years) without evidence of neurodegenerative disease. They also aimed to assess whether the pattern of P-SYN deposition was a predictor of future phenoconversion to a clinically definite synucleinopathy.

The Syn-One Test measures the presence of intra-neuronal P-SYN through a simple in-office skin punch biopsy procedure. With this test, investigators take 3 biopsies: the neck, around the knee, and around the ankle. Investigators identified the nerves in the dermal layer and the protein P-SYN.

The test detected P-SYN in 75% participants with iRBD. Those with detected P-SYN tended to be older (68.7±7.6 years) than those without detected P-SYN (63.8±11.9 years).

Levine suspects that phosphorylation causes misfolding of those proteins, and these proteins build up around the nerve, eventually becoming toxic and leading to the death of those nerves.

It has been known for a while that patients with RBD have a greater incidence of developing diseases in the synuclein family, like Parkinson Disease. Additionally, other research has shown that P-SYN detection is possible in patients with RBD, which most likely suggests that these patients are likely to develop neurogenerative diseases.

DaTscans have been used to detect P-SYN in patients with RBD. Spinal fluid has also been examined to detect P-SYN.

“What's really unique now is that this skin-based test is very convenient. It's done in a doctor's office,” Levine said. “[This test] really has increased the access to the early detection of this pathological protein in patients with REM behavior disorder.”

Relevant disclosures for Levine include Biogen, UCB, Regeneron Pharmaceuticals, Janssen Research & Development, ARGENX US, Sanofi and Genzyme US Companies, Merck KGaA, Alexion Pharmaceuticals, Mitsubishi Tanabe Pharma America, and Genentech.

References

1. Levine T, Bellaire B, Gibbons C, et al. THE SYN-SLEEP STUDY: DETECTION OF CUTANEOUS PHOSPHORYLATED ALPHA-SYNUCLEIN IN REM SLEEP BEHAVIOR DISORDER. Presented at SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies, in Seattle.

2. CND Life Sciences’ Syn-One Test® Detects Alpha-Synuclein in Skin Biopsies of Patients with REM Sleep Behavior Disorder. CND Life Sciences. June 5, 2025. https://cndlifesciences.com/syn-sleep-baseline/. Accessed June 24, 2025.