Seminar – Tanya Simuni

Venue: Centre Broca

Pr. Tanya Simuni, MD, FAAN

Invited by Wassilios Meissner (IMN)

Title

Abstract

A biologic research definition and staging framework for neuronal alpha‑synucleinopathies, including Parkinson’s disease and dementia with Lewy bodies, is essential for improving clinical trial design and accelerating therapeutic development. Neuronal Synuclein Disease (NSD) and its companion Integrated Staging System (NSD‑ISS) represent a biologic definition and staging construct developed collaboratively by stakeholders across academia, industry, advocacy organizations, and, importantly, individuals with lived experience. Much of this framework has been informed and enabled by insights generated through the Parkinson’s Progression Markers Initiative (PPMI). This talk will summarize the key concepts of the current NSD‑ISS, highlight the latest expanded biomarker initiatives within PPMI, and outline plans for the next iteration of NSD‑ISS based on emerging knowledge.

The second part of the talk will describe The Path to Prevention Platform Trial (P2P), a multi‑center, multi‑regimen, proof‑of‑concept, phase 2A randomized clinical trial designed to evaluate the safety and early efficacy of investigational therapeutics for individuals in the Early‑Stage NSD population. P2P is embedded within PPMI, meaning its conceptualization, design, and implementation are driven by learnings from the PPMI study. P2P represents an important step toward defining the clinical trial and regulatory pathways for interventions targeting early‑stage NSD.

Biosketch

My major contribution to science is international leadership in advancement of translational science in the development of therapeutics for slowing progression of Parkinson’s disease. I have extensive expertise in clinical research, including design and conduct of single- and multicenter studies in early PD. Under my leadership, we completed the Phase 3 multicenter isradipine study (STEADY-PD3) across 56 sites. I have served as PI on multicenter Phase 2 PD trials (e.g., NILO-PD) and more than 30 other projects. I am Site PI and on the Leadership Team for PPMI, lead planning for the Path to Prevention platform in prodromal PD, and co-lead the international working group defining and staging Neuronal Synuclein Disease (NSD). I also lead the NeuroNEXT (NEXT) Northwestern Clinical Site and serve on governance bodies for PD genetics and prevention initiatives.

Publications

1. Brooker SM, Pasquini J, Choi SH, Simuni T, et al. Clinical and Imaging Characteristics of Parkinson’s Disease with Negative Alpha-Synuclein Seed Amplification Assay. Mov Disord 2026 20260128. DOI: 10.1002/mds.70197.
2. Chahine LM, Lafontant DE, Choi SH..Simuni, T. LRRK2-associated parkinsonism with and without in vivo evidence of alpha-synuclein aggregates: longitudinal clinical and biomarker characterization. Brain Commun 2025; 7: fcaf103. 20250306. DOI: 10.1093/braincomms/fcaf103.
3. Coughlin DG, Adler CH, Barbosa W, Simuni, T, et al. CSF alpha-Synuclein Seed Amplification Assays and Skin Immunofluorescence: Clinical Applications, Research Opportunities, and Knowledge Gaps. Neurology 2026; 106: e214648. 20260113. DOI: 10.1212/WNL.0000000000214648.
4. Cousins KAQ, Irwin DJ, Tropea TF, Simuni, T et al. Evaluation of ATN(PD) Framework and Biofluid Markers to Predict Cognitive Decline in Early Parkinson Disease. Neurology 2024; 102: e208033. 20240202. DOI: 10.1212/WNL.0000000000208033.
5. Dam T, Pagano G, Brumm MC, ,,Simuni, T. Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts. NPJ Parkinsons Dis 2024; 10: 178. 20240927. DOI: 10.1038/s41531-024-00789-w.
6. Kopal J, Vo A, Tao Q, Simuni, T, et al. Carriers of LRRK2 pathogenic variants show a milder, anatomically distinct brain signature of Parkinson’s disease. Commun Med (Lond) 2026; 6: 71. 20260103. DOI: 10.1038/s43856-025-01330-7.
7. Lashuel HA, Surmeier DJ, Simuni T, et al. Alpha-synuclein seed amplification assays: Data sharing, standardization needed for clinical use. Sci Adv 2025; 11: eadt7195. 20250402. DOI: 10.1126/sciadv.adt7195.
8. Mammen JR, Adams JL, Mangrum R,..Simuni, T. Systematic review and consensus conceptual model of meaningful symptoms and functional impacts in early Parkinson’s Disease. NPJ Parkinsons Dis 2025; 11: 65. 20250403. DOI: 10.1038/s41531-025-00907-2.
9. Marras C, Fereshtehnejad SM, Berg D, Simuni, Tet al. Transitioning from Subtyping to Precision Medicine in Parkinson’s Disease: A Purpose-Driven Approach. Mov Disord 2024; 39: 462-471. 20240120. DOI: 10.1002/mds.29708.
10. Mestre TA, Stebbins GT, Stephenson D, Simuni, T et al. Patient-centered development of clinical outcome assessments in early Parkinson disease: key priorities and advances. NPJ Parkinsons Dis 2024; 10: 101. 20240514. DOI: 10.1038/s41531-024-00716-z.
11. Simuni T, Chahine LM, Poston K, et al. A biological definition of neuronal alpha-synuclein disease: towards an integrated staging system for research. Lancet neurology 2024; 23: 178-190. DOI: 10.1016/S1474-4422(23)00405-2.
12. Simuni T, Gochanour C, Nair AR, et al. Neuronal alpha-Synuclein Disease Stage Progression over 5 Years. Mov Disord 2025; 40: 1318-1330. 20250430. DOI: 10.1002/mds.30191.