On Wednesday morning, CND Life Sciences presented exciting new data at SLEEP 2026 from the NIH-sponsored Syn-Sleep Study, indicating that its Syn-One Test detected phosphorylated alpha-synuclein (P-SYN) in 75% of patients with idiopathic REM sleep behavior disorder (RBD).
SleepWorld had a chance to sit down with CND Chief Medical Officer and Co-Founder Todd Levine, MD, to talk about the significance of these findings.
“I think most people that treat sleep are aware that RBD carries a risk of developing a neurodegenerative disease,” Dr. Levine said. “Not all RBD is the same, in the same way that not all Parkinson’s is the same. Understanding that your patient has RBD with synuclein carries a different set of issues than your patient who has RBD without synuclein — and the Syn-One Test is a very convenient way to get that answer.”
“We were excited that the data showed it’s both sensitive and specific in detecting people that are accumulating the alpha-synuclein protein,” he said.
Study Introduction: Isolated REM sleep behavior disorder (iRBD) is a prodromal neurodegenerative disease characterized by dream reenactment and REM sleep atonia. Pathologically, there is deposition of phosphorylated alpha-synuclein (P-SYN) within the central and peripheral nervous system of patients with iRBD. There is a high risk of phenoconversion from iRBD to a clinically apparent synucleinopathy (Parkinson’s disease (PD), multiple system atrophy (MSA), or dementia with Lewy bodies (DLB)), with >73% of patients phenoconverting over 12 years.
Study objectives:
1) determine rates of P-SYN deposition in patients with iRBD
2) quantifychanges in P-SYN deposition over time
3) determine if patterns of P-SYN deposition predict phenoconversion to a specific synucleinopathy subtype
Methods: Patients with iRBD (confirmed by polysomnography or validated questionnaire and history) were included in this prospective, blinded multicenter study. Detailed examinations, orthostatic vital signs, and questionnaires were completed. Medical history, ancillary testing, and polysomnograms (PSG) were reviewed, if applicable. Skin biopsies at the distal leg, distal thigh, and posterior cervical sites were collected. Dual immunohistochemical immunostaining for nerve fibers (protein gene product 9.5) and P-SYN were completed with blinded pathological assessment.
Results: 80 subjects (31% female, age 67.8±8.7 years) were enrolled. P-SYN was detected in 75% (60/80) of subjects at baseline. In a preliminary analysis of the first 49 patients to complete 12-month follow-up, the average P-SYN score at baseline was 4.06±4.51, and at the 12-month follow-up was 5.53±5.38 (p>0.05). Four patients who were P-SYN negative at baseline became positive at 12 months. All individuals initially positive for P-SYN remained positive at 12 months. No complications were noted in the biopsy procedure.
Conclusion: Skin biopsy is a safe and highly sensitive method for the detection of P-SYN in prodromal disease. Our quantitative analysis of P-SYN revealed a 36% increase over 12 months. Ongoing longitudinal follow-up will determine if P-SYN deposition patterns can predict both time to phenoconversion and synucleinopathy subtype.
Support: NIH R44NS127696
Todd Levine 1 , Bailey Bellaire 1 , Sarrah Marcotte 1 , Jourdan Parent 1 , Manuel Duval 1 , Roy Freeman 1,2 , Christopher Gibbons 1,2
1. CND Life Sciences, Scottsdale, AZ.
2. Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
