Abstract Details

Title The Synuclein-One Study: Skin Biopsy Detection of Phosphorylated alpha-synuclein for Diagnosis of the Synucleinopathies

Topic Movement Disorders

Presentation(s) S37 - Movement Disorders: Phenotyping and Biomarkers (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Background The Synuclein-One study is an ongoing NIH-funded 30-site multicenter trial of ~400 patients with synucleinopathies including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA) and pure autonomic failure (PAF). Enrollment will close in December 2022, with final data analysis 2/1/2022.

Objective To describe the sensitivity, specificity, accuracy and precision of skin biopsy to detect the presence of phosphorylated alpha-synuclein in patients with synucleinopathies.

Design/Methods After signing informed consent, all subjects will complete detailed neurologic examinations (MDS-UPDRS, Hoehn and Yahr scale), detailed disease history review, cognitive evaluation (MOCA), orthostatic vital signs, RBD questionnaire, orthostatic hypotension questionnaire, MSA red flags and Parkinson’s Disease Questionnaire-39. All subjects will complete skin biopsies at the distal leg, distal thigh and proximal thigh. All clinical material will be reviewed by a blinded expert consensus panel to confirm the referring diagnosis or move to an ‘indeterminate’ category. Skin biopsies will be processed at 2 independent laboratories. Phosphorylated alpha-synuclein deposition will be quantified by 2 readers, blinded to referring diagnosis and results of the other reader.

Results Final un-blinded results will be presented at the AAN 2023 annual meeting with a focus on sensitivity, specificity, accuracy and precision. In addition, synucleinopathy subgroup analysis will be performed to define unique pathological characteristics of disease (PD, MSA, DLB or PAF).

Conclusions The need for a validated, well-characterized, simple, reproducible marker of synuclein pathology has never been greater. The number of individuals with neurodegenerative diseases continues to grow and misdiagnosis within and among synuclein and non-synuclein pathologies continues to occur, resulting in incorrect medication choices, iatrogenic complications, poor prognostication and patient frustration. The Synuclein-One study is the largest investigation of cutaneous phosphorylated alpha-synuclein detection across all four synucleinopathies and will advance the field of neuro-diagnostic testing in neurodegenerative disease.

Authors/Disclosures
Christopher H. Gibbons, MD, FAAN (Beth Israel Deaconess Medical Center) PRESENTER	Dr. Gibbons has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Autonomic Neuroscience. Dr. Gibbons has stock in CND Life Sciences. Dr. Gibbons has received publishing royalties from a publication relating to health care. Dr. Gibbons has received personal compensation in the range of $5,000-$9,999 for serving as a Expert Advisor with Department of Justice.
	No disclosure on file
Ningshan Wang, MD, PhD (BIDMC)	Dr. Wang has nothing to disclose.
Roy L. Freeman, MD (Beth Israel Deaconess Hosp)	Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Regenacy. Dr. Freeman has received personal compensation in the range of $100,000-$499,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurobo. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli-Lilly. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theravance. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Inhibikase. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Freeman has stock in Neurobo. Dr. Freeman has stock in Cutaneous NeuroDiagnostics. The institution of Dr. Freeman has received research support from NIH. The institution of Dr. Freeman has received research support from Theravance. The institution of Dr. Freeman has received research support from Biohaven. The institution of Dr. Freeman has received research support from Lundbeck.
Charles H. Adler, MD, PhD, FAAN (Mayo Clinic Arizona)	Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avion. Dr. Adler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CND Life Sci. Dr. Adler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Jazz. Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Precon. Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. The institution of Dr. Adler has received research support from NIH. The institution of Dr. Adler has received research support from Michael J. Fox Foundation. The institution of Dr. Adler has received research support from Arizona Biomedical Research Commission. Dr. Adler has received publishing royalties from a publication relating to health care.
Mitchell G. Miglis, MD, FAAN (Stanford University Medical Center)	Dr. Miglis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Infinite MD. Dr. Miglis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint, LLC. Dr. Miglis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for 2nd MD. Dr. Miglis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MED-IQ. Dr. Miglis has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Van Cott and Talamante. Dr. Miglis has received publishing royalties from a publication relating to health care.
Stuart H. Isaacson, MD, FAAN (Parkinson's Dis & Mov Dis Ctr of Boca Raton)	The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acadia. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sunovion. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for acorda. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Supernus. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurocrine. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kyowa. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for adamas. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neuroderm. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. The institution of Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for amneal. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurocrine. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for adamas. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Lundbeck. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Supernus. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acadia. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amneal. Dr. Isaacson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbvie.
Virgilio Gerald H. Evidente, MD, FAAN (Movement Disorders Center of Arizona)	Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revance. Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Evidente has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Evidente has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Ipsen. Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medtronic. Dr. Evidente has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurocrine. The institution of Dr. Evidente has received research support from Neuraly. The institution of Dr. Evidente has received research support from CND. The institution of Dr. Evidente has received research support from Aptinyx. The institution of Dr. Evidente has received research support from Aeon. The institution of Dr. Evidente has received research support from Bukwang Pharmaceuticals. The institution of Dr. Evidente has received research support from Jazz Pharmaceuticals. The institution of Dr. Evidente has received research support from Scion Neurostim. The institution of Dr. Evidente has received research support from Theravance Biopharma. Dr. Evidente has received research support from Cerevance. Dr. Evidente has received research support from Ipsen.
Michael Soileau, MD, FAAN (Texas Movement Disorder Specialists, PLLC)	The institution of Dr. Soileau has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbott. The institution of Dr. Soileau has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Medtronic. The institution of Dr. Soileau has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. The institution of Dr. Soileau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. The institution of Dr. Soileau has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine PHarmaceuticals. The institution of Dr. Soileau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal Pharmaceuticals. Dr. Soileau has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Abbvie. Dr. Soileau has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amneal. Dr. Soileau has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kiran. The institution of Dr. Soileau has received research support from Abbvie. The institution of Dr. Soileau has received research support from Cerevel. The institution of Dr. Soileau has received research support from Praxis. The institution of Dr. Soileau has received research support from CND Life Sciences. The institution of Dr. Soileau has received research support from Teva. The institution of Dr. Soileau has received research support from Abbott. The institution of Dr. Soileau has received research support from Jazz Pharmaceuticals. The institution of Dr. Soileau has received research support from Scion. Dr. Soileau has received publishing royalties from a publication relating to health care.
Mark Gudesblatt, MD (South Shore Neurology Assoc. PC)	No disclosure on file
Guillaume Lamotte, MD	Dr. Lamotte has nothing to disclose.
Rajeev Kumar, MD, FRCPC (Rocky Mountain Movement Disorders Center)	The institution of Dr. Kumar has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Supernus. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. The institution of Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Teva Pharmaceuticals. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Annexon. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cerevel Therapeutics. Dr. Kumar has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel Pharma. Dr. Kumar has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Supernus. The institution of Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Teva. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Kumar has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Research Catalyst, LLC. Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for CenExel RMCR. Dr. Kumar has stock in Research Catalyst, LLC. Dr. Kumar has stock in CenExel. The institution of Dr. Kumar has received research support from Supernus. The institution of Dr. Kumar has received research support from Sage Therapeutics. The institution of Dr. Kumar has received research support from Prilenia Therapeutics. The institution of Dr. Kumar has received research support from Roche. The institution of Dr. Kumar has received research support from Triplet Therapeutics. The institution of Dr. Kumar has received research support from CHDI Foundation. The institution of Dr. Kumar has received research support from Neurocrine Biosciences. The institution of Dr. Kumar has received research support from Biovie. The institution of Dr. Kumar has received research support from Neuroderm. The institution of Dr. Kumar has received research support from Sanofi. The institution of Dr. Kumar has received research support from Addex Pharma. The institution of Dr. Kumar has received research support from Integrative Research Laboratories. The institution of Dr. Kumar has received research support from Takeda Pharmaceuticals. The institution of Dr. Kumar has received research support from Neuraly. The institution of Dr. Kumar has received research support from Abbvie. The institution of Dr. Kumar has received research support from Cerevel Therapeutics. The institution of Dr. Kumar has received research support from Transposon Therapeutics. The institution of Dr. Kumar has received research support from Lundbeck. The institution of Dr. Kumar has received research support from Biohaven. The institution of Dr. Kumar has received research support from Revance Therapeutics. The institution of Dr. Kumar has received research support from Impax Laboratories. The institution of Dr. Kumar has received research support from Pharma Two B. The institution of Dr. Kumar has received research support from Enterin. The institution of Dr. Kumar has received research support from CND Life Sciences. The institution of Dr. Kumar has received research support from Neuron23. The institution of Dr. Kumar has received research support from Annexon Biosciences. The institution of Dr. Kumar has received research support from Annovis. The institution of Dr. Kumar has received research support from PTC Therapeutics. The institution of Dr. Kumar has received research support from Uniqure. The institution of Dr. Kumar has received research support from Alexza. The institution of Dr. Kumar has received research support from SparkNeuro. The institution of Dr. Kumar has received research support from Praxis. The institution of Dr. Kumar has received research support from Scion Neurostim. The institution of Dr. Kumar has received research support from Cognition Therapeutics. The institution of Dr. Kumar has received research support from Eli Lilly. Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as a Medical Director with CenExel RMCR. Dr. Kumar has received personal compensation in the range of $1,000,000+ for serving as a Managing Member with Research Catalyst, LLC.
Melita T. Petrossian, MD (Pacific Movement Disorders Center)	An immediate family member of Dr. Petrossian has received personal compensation for serving as an employee of Nile AI. An immediate family member of Dr. Petrossian has received personal compensation for serving as an employee of Neurolutions. Dr. Petrossian has received personal compensation for serving as an employee of Kandu Health. Dr. Petrossian has stock in Kandu Health. An immediate family member of Dr. Petrossian has stock in Nile AI. An immediate family member of Dr. Petrossian has stock in Neurolutions. An immediate family member of Dr. Petrossian has stock in Nova Signal. An immediate family member of Dr. Petrossian has stock in Imperative Care. The institution of Dr. Petrossian has received research support from Praxis. The institution of Dr. Petrossian has received research support from NIH.
Maria Alejandra Gonzalez Duarte, MD, FAAN (NYU Dysautonomia Center)	Dr. Gonzalez Duarte has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alnylam. Dr. Gonzalez Duarte has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca. Dr. Gonzalez Duarte has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Anylam . The institution of Dr. Gonzalez Duarte has received research support from Pfizer.
Pravin Khemani, MD, FAAN (Swedish Neuroscience Institute)	Dr. Khemani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Scientific. Dr. Khemani has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cala Trio. Dr. Khemani has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurocrine.
Marie-Helene Saint-Hilaire, MD, FRCPC, FAAN (Boston University School of Medicine)	Dr. Saint-Hilaire has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acorda. Dr. Saint-Hilaire has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Altec. Dr. Saint-Hilaire has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Watermark. Dr. Saint-Hilaire has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Parkinson study group.
Nikolaus McFarland, MD, PhD, FAAN (University of Florida)	Dr. McFarland has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sutter Health. The institution of Dr. McFarland has received research support from NIH. Dr. McFarland has received publishing royalties from a publication relating to health care.
HEMANT PANDEY, MD (Brain and Spine Center)	Dr. Pandey has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for BIOHAVEN.
Oleg Y. Yerstein, MD (Lahey Hospital & Medical Center)	Dr. Yerstein has nothing to disclose.
Alexandru C. Barboi, MD (IU Health Neuroscience Center)	Dr. Barboi has nothing to disclose.
Andrew Liu, MD (Duke Health)	Dr. Liu has received personal compensation in the range of $0-$499 for serving as a Consultant for Darwin Research Group.
Todd D. Levine, MD (Honor Health)	Dr. Levine has received personal compensation for serving as an employee of CND life sciences . Dr. Levine has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Nufactor. Dr. Levine has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Grifols. Dr. Levine has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for PNA. Dr. Levine has stock in CND Life Sciences. Dr. Levine has stock in Corinthian reference lab.