Congress: Movement Disorder Society (MDS) International Congress 2026
Dates: October 4-8, 2026
Location: Seoul, Korea — COEX Convention and Exhibition Center
Theme: Understanding Aging in Movement Disorders
Levodopa-induced dyskinesias (LID) represent one of the most debilitating complications of long-term Parkinson's disease (PD) treatment, developing in approximately 40-50% of patients within 4-6 years of levodopa initiation and up to 90% after 10 years of continuous treatment[1]. These involuntary movements significantly impact quality of life, functional independence, and often limit the ability to optimize dopaminergic therapy.
MDS 2026 showcases significant advances in understanding LID pathophysiology and a comprehensive toolkit of management strategies ranging from pharmacological optimization to surgical interventions and emerging disease-modifying approaches.
| Parameter | Value |
|---|---|
| 5-year incidence | 40-50% of levodopa-treated patients |
| 10-year incidence | Up to 90% |
| Peak-dose dyskinesias | Most common type (~70% of LID) |
| Diphasic dyskinesias | ~15-20% of cases |
| Off-period dystonia | ~25% of cases |
Disease-related factors:
Treatment-related factors:
Genetic susceptibility:
The development of LID involves multiple interconnected mechanisms:
| Pathway | Role in LID | Therapeutic Target |
|---|---|---|
| ERK1/2 signaling | Promotes aberrant synaptic plasticity | MEK inhibitors |
| mTOR pathway | Drives protein synthesis in dyskinesia | Rapamycin, everolimus |
| DARPP-32 | Amplifies D1 receptor signaling | PP1 inhibitors |
| GluA2 subunit editing | Increases AMPA receptor permeability | AMPA modulators |
| 5-HT neurons | 充当非生理性多巴胺来源 | 5-HT1A agonists |
The foundational theory explains LID as a consequence of non-physiological, pulsatile dopamine receptor activation from oral levodopa dosing. This contrasts with the continuous dopamine signaling that occurs in the healthy basal ganglia. Continuous dopaminergic delivery (CDD) strategies aim to restore more physiological stimulation patterns[2].
Amantadine remains the only FDA-approved pharmacological agent specifically indicated for LID:
| Formulation | Dose | Key Features |
|---|---|---|
| Immediate-release | 100mg twice daily | Original formulation |
| Gocovri (ER) | 274mg once daily (bedtime) | FDA-approved for LID specifically |
| Osmolex ER | 274mg once daily | Generic extended-release |
Mechanism: Non-competitive NMDA receptor antagonism in the striatum, reducing glutamatergic overactivity in the subthalamo-pallidal pathway.
Efficacy:
Considerations:
| Agent | Mechanism | Effect on LID | Evidence Level |
|---|---|---|---|
| Entacapone | COMT inhibitor | May reduce via improved levodopa availability | Moderate |
| Opicapone | COMT inhibitor | Once-daily, superior to entacapone | High |
| Entacapone + levodopa | Triple combination | More stable plasma levels | High |
| Dopamine agonists (ropinirole, pramipexole) | D2/D3 agonists | Allow levodopa dose reduction | Moderate |
| Safinamide | MAO-B + Na+ channel | May reduce motor fluctuations | Moderate |
DBS is the most effective intervention for management of advanced PD with motor complications, including LID[5]:
| Target | LID Reduction | Motor Symptoms | Cognitive Risk |
|---|---|---|---|
| STN | 50-70% | Excellent | Higher than GPi |
| GPi | 40-60% | Good | Lower |
| Combined STN+GPi | 60-80% | Excellent | Moderate |
Key findings from MDS 2026:
Commercially known as Duodopa or Duopa (jejunal infusion):
| Parameter | Value |
|---|---|
| LID reduction | 60-70% |
| "Off" time reduction | 4-5 hours/day |
| Quality of life improvement | 20-30% on PDQ-39 |
| Parameter | Value |
|---|---|
| LID reduction | 40-60% |
| "Off" time reduction | 2-3 hours/day |
| Delivery method | Continuous SC infusion |
| Agent | Status | Mechanism |
|---|---|---|
| ABBV-951 (Crexont) | Approved 2024 | Subcutaneous foslevodopa/foscarbidopa |
| Travis-1012 | Phase III | Oral levodopa prodrug |
| TN-101 | Phase II | Extended-release oral |
These formulations aim to provide more continuous levodopa delivery, potentially reducing LID development when used early.
| Target | Approach | Stage |
|---|---|---|
| AAV-TH | Deliver tyrosine hydroxylase gene | Phase II |
| AAV-AADC | Deliver aromatic L-amino acid decarboxylase | Phase II |
| AAV-GAD | Deliver glutamic acid decarboxylase to STN | Phase I/II |
These approaches aim to restore endogenous dopamine synthesis, potentially enabling discontinuation of oral levodopa and preventing LID.
Given that preventing LID is superior to treating it:
LID significantly affects multiple domains:
| Domain | Impact | Assessment Tool |
|---|---|---|
| Physical | Involuntary movements, fatigue | UDysRS, MDS-UPDRS IV |
| Psychological | Embarrassment, anxiety, depression | PDQ-39, Beck Depression Inventory |
| Social | Social isolation, dependency | PDQ-39 social subscale |
| Functional | Eating, walking, dressing | Schwab & England ADL |
| Agent | Mechanism | Phase | Expected Timeline |
|---|---|---|---|
| Eltoprazine | 5-HT1A/1B agonist | Phase II/III | 2026-2027 |
| ABBV-951 | SC levodopa delivery | Approved | Now |
| Gene therapy (AAV-AADC) | AADC gene delivery | Phase II | 2027-2028 |
| Stem cell therapy | Dopamine neuron replacement | Phase I/II | 2028+ |
Jankovic J (2005). Motor fluctuations and dyskinesias in Parkinson's disease. Mov Disord. 2005. ↩︎
Castriotoa A, et al. (2013). Maladaptive-plasticity in Parkinson's disease. J Neural Transm. 2013. ↩︎
Hauser RA, et al. (2023). Amantadine for levodopa-induced dyskinesia in Parkinson's disease. Neurology. 2023. ↩︎
Fox SH, et al. (2018). International Parkinson's and Movement Disorders Society evidence-based review of treatments for Parkinson's disease motor complications. Mov Disord. 2018. ↩︎
Pagonabarraga J, et al. (2015). Deep brain stimulation for Parkinson's disease. Mov Disord. 2015. ↩︎