Movement Disorders | Unravelling Mechanisms and Improving Therapeutics*
Date: October 20, 2026
Time: 11:00 am to 12:30 pm
Room: Coral 3
Track: Traditional Special Interest Group (SIG)
Session Description
The 2026 Movement Disorders Special Interest Group session highlights a shift from phenotype-based classification to biologically driven, mechanism-based frameworks that are shaping therapeutic development. Advances in molecular genetics, proteinopathies, and systems neuroscience are redefining disease heterogeneity, progression, and treatment response across disorders such as dystonia, Parkinson’s disease (PD), and progressive supranuclear palsy (PSP).
This session will feature leaders in mechanistic discovery, biomarker development, and innovative clinical trial design. Topics will include molecular stratification in dystonia, genetic and lysosomal pathways in PD, and the role of tau pathology in cognitive and neuropsychiatric features. In addition, emerging platform trial designs in PSP will be discussed as scalable models for evaluating disease-modifying therapies. Attendees will gain a forward-looking framework for integrating biologic insights into clinical care and research in movement disorders.
Learning Objectives
At the conclusion of this session, attendees will be able to:
- Describe emerging biologic mechanisms in movement disorders and their role in redefining disease classification.
- Apply biomarker and genetic insights to enhance patient stratification and inform clinical trial design.
- Integrate principles of precision neurology into clinical practice for diagnosis, prognosis, and management.
Speakers
- (Chair) Chi-Ying “Roy” Lin, MD, FAAN, MPH
- (Co-Chair) Joohi Jimenez-Shahed, MD, FANA
- (Speaker) Anne-Marie Wills, MD, MPH
- (Speaker) Nicole Calakos, MD, PhD, FANA
- (Speaker) Joshua Shulman, MD, PhD
- (Speaker) Kathleen Poston, MD, MS, FAAN, FANA
- (Speaker) David Lynch, MD, PhD, FANA (2026 SIG Oral Presenter)
PSP National Platform Trial Development and Initiation
Description
Progressive supranuclear palsy (PSP) is a rare, rapidly progressive neurodegenerative disorder for which effective disease-modifying therapies remain an unmet need. Innovative clinical trial designs, including platform trials, have the potential to accelerate therapeutic development by efficiently evaluating multiple investigational treatments within a single research framework.
This presentation will provide an update on the development and launch of the PSP National Platform Trial. Participants will review the rationale and design of the platform trial, examine the process for selecting investigational compounds, and discuss early implementation milestones, including site activation and initial patient enrollment. Topics will also include the landscape of tau-targeted therapies in development for PSP.
Attendees will leave with a greater understanding of the current PSP clinical trial landscape and practical insights into how platform trial methodologies are shaping the future of therapeutic development for progressive supranuclear palsy.
Are Dystonias Ready for Molecular Pathophysiological Groupings? The Case for the Integrated Stress Response
Description
In this presentation, Dr. Calakos will explore how human genetic and preclinical studies highlight potential mechanistic connections across dystonias that have historically been considered in isolation.
GBA1 and Lysosomal Oligogenic Risk for Parkinson’s Disease
Description
Mutations in **GBA1** represent one of the most important genetic risk factors for Parkinson’s disease, yet not all carriers develop the disease, suggesting that additional genetic modifiers influence disease susceptibility. Increasing evidence supports an oligogenic model in which interactions among multiple lysosomal genes contribute to disease risk, progression, and phenotypic variability.
This presentation will explore how cross-species genetic studies have advanced our understanding of GBA1-associated Parkinson’s disease by demonstrating that disease penetrance is modified by variation in other lysosomal genes. Participants will review the evidence supporting an oligogenic model of Parkinson’s disease, examine the biological mechanisms linking lysosomal dysfunction to neurodegeneration, and discuss how these findings are reshaping our understanding of genetic risk and disease pathogenesis. Topics will also include the implications of these discoveries for genetic risk assessment, precision medicine, and the development of targeted therapeutic strategies.
Attendees will leave with a greater understanding of the complex genetic architecture underlying Parkinson’s disease and practical insights into how lysosomal gene interactions may inform future approaches to disease prediction, patient stratification, and therapeutic development.
Mixed Pathology is the Rule: Emerging Biomarkers to Assess the Impact of Amyloid and Tau on Clinical Progression in Parkinson’s Disease
Description
Mixed proteinopathies are increasingly recognized as the norm rather than the exception in neurodegenerative disease. In Parkinson’s disease and dementia with Lewy bodies, coexisting Alzheimer’s disease pathology—particularly amyloid and tau deposition—can significantly influence cognitive decline, functional outcomes, and disease progression, underscoring the need for biomarkers that enable earlier risk stratification and personalized care.
This presentation will examine the role of emerging biomarkers in assessing the impact of amyloid and tau pathology on the clinical progression of Parkinson’s disease. Participants will review evidence from cerebrospinal fluid and positron emission tomography (PET) studies demonstrating the high prevalence of coexisting Alzheimer’s disease neuropathology in individuals with Lewy body disorders. Topics will then include recent advances in plasma biomarkers, emphasizing their application in large-scale and longitudinal studies to predict cognitive and functional decline, stratify patient risk, and monitor disease progression. The clinical implications of these biomarkers for prognosis, patient selection, and future therapeutic trials will also be discussed.
Attendees will leave with a greater understanding of the importance of mixed neuropathology in Parkinson’s disease and practical insights into how emerging plasma biomarkers can improve prognostic assessment, facilitate precision medicine approaches, and support the development of targeted disease-modifying therapies.
DT-216P2, a Gene-Targeted Small Molecule, Produces Rapid Dose-Dependent Clinical Improvements and Comprehensive Frataxin Biomarker Activity in Friedreich Ataxia: RESTORE-FA 4-week IV Cohorts Results
Description
Friedreich ataxia (FA) is a progressive, inherited neurodegenerative disorder caused by reduced frataxin expression resulting from expanded GAA repeat sequences in the *FXN* gene. Novel gene-targeted therapies that restore endogenous frataxin expression offer a promising strategy for addressing the underlying genetic cause of the disease.
This presentation will review findings from the RESTORE-FA Phase 2 study evaluating DT-216P2, a first-in-class bifunctional small molecule designed to bind expanded GAA repeats and recruit the transcriptional machinery to restore endogenous frataxin expression. Participants will examine clinical and biomarker results from the initial four-week intravenous dosing cohorts, including evidence of rapid, dose-dependent improvements across multiple clinical and molecular endpoints. Topics will also include the mechanism of action of DT-216P2, changes in frataxin biomarkers, treatment effects observed in participants receiving background omaveloxolone therapy, and the implications of these findings for the future of gene-targeted therapies in Friedreich ataxia.
Attendees will leave with a greater understanding of this novel gene-targeted therapeutic approach and practical insights into how restoring endogenous frataxin expression may advance disease-modifying treatment strategies for individuals with Friedreich ataxia.
