Therapeutic Strategies for Advanced Parkinson's Disease

Advanced Parkinson’s disease presents with motor fluctuations, disabling dyskinesias and progressive non-motor features that often prove refractory to conventional oral therapy. Central to management is optimisation of levodopa delivery and the use of adjunctive pharmacological agents to smooth plasma dopamine levels. Device-aided interventions include deep brain stimulation of basal ganglia targets, which can provide sustained motor benefit and reduce medication burden, and continuous infusion therapies, in which levodopa/carbidopa intestinal gel or subcutaneous apomorphine bypasses erratic gastrointestinal absorption. Transdermal patches and inhaled formulations offer non-invasive alternatives aimed at rapid rescue from OFF periods. Patient selection is guided by the pattern of motor complications, cognitive status and personal goals, with shared decision-making improving adherence and satisfaction. Looking beyond symptomatic control, emerging approaches explore neuroprotective and restorative strategies such as gene therapy to enhance dopaminergic transmission, cell-replacement with stem-cell derived neurons and focused ultrasound ablation of dysregulated circuits. A holistic strategy also addresses non-motor symptoms through autonomic, psychiatric and rehabilitative interventions. Together, these multidisciplinary approaches aim to prolong functional independence, improve quality of life and tailor therapy to individual risk–benefit profiles.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Therapeutic Strategies for Advanced Parkinson's Disease publication trend

The graph below shows the total number of articles in therapeutic strategies for advanced parkinson's disease across all publications each year (not limited to Nature Index journals).

Technical terms

Motor fluctuations: Variations between periods of good motor control (ON) and poor mobility (OFF) arising from levodopa pharmacokinetics.

Deep Brain Stimulation (DBS): Surgical implantation of electrodes in basal ganglia targets to modulate pathological neural activity and improve motor symptoms.

Continuous Subcutaneous Apomorphine Infusion (CSAI): Steady delivery of a dopamine agonist via a subcutaneous pump to reduce OFF time and motor fluctuations.

Levodopa/Carbidopa Intestinal Gel (LCIG): Direct jejunal infusion of levodopa combined with carbidopa to maintain consistent plasma levels and attenuate dyskinesia.

OFF time: Periods during which antiparkinsonian medication fails to provide adequate symptom relief, leading to bradykinesia and rigidity.

References

1. Selecting deep brain stimulation or infusion therapies in advanced Parkinson’s disease: an evidence-based review. Journal of Neurology (2013).
2. Long-term safety and efficacy of apomorphine infusion in Parkinson's disease patients with persistent motor fluctuations: Results of the open-label phase of the TOLEDO study. Parkinsonism & Related Disorders (2021).
3. ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with Parkinson's disease and motor response fluctuations: A randomized, placebo-controlled phase 2 study. Parkinsonism & Related Disorders (2021).
4. Non-oral dopaminergic therapies for Parkinson’s disease: current treatments and the future. npj Parkinson's Disease (2016).
5. The Patient's Perspective on Shared Decision-Making in Advanced Parkinson's Disease: A Cross-Sectional Survey Study. Frontiers in Neurology (2019).