October Young Researcher Highlight 
Continuous subcutaneous foslevodopa-foscarbidopa in Parkinson's disease: A mini-review of current scope and future outlook

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Parkinson's disease (PD) is a complex and progressive neurodegenerative disorder characterized by debilitating motor and non-motor symptoms, primarily driven by dopaminergic neuronal degeneration. While oral levodopa has long been the cornerstone of PD treatment, its long-term use often leads to motor fluctuations and dyskinesias, highlighting the need for alternative therapies. Continuous dopaminergic stimulation (CDS) is increasingly recognized as a crucial approach in managing advanced PD, offering more stable symptom control compared to intermittent oral administration. 

Our mini-review focuses on foslevodopa-foscarbidopa, an innovative prodrug combination designed for continuous subcutaneous infusion, as a promising alternative for CDS. These prodrugs exhibit excellent chemical stability, solubility, and pharmacokinetics, enabling sustained and stable plasma concentrations of levodopa and carbidopa. This delivery method addresses the limitations of oral therapies by reducing motor fluctuations and "off time," while improving "on time" without troublesome dyskinesias. 

Clinical trials have demonstrated the efficacy of foslevodopa-foscarbidopa in advanced PD. Phase III studies reported significant improvements in motor symptom control, with an increase in "on time" of up to 2.75 hours compared to oral levodopa-carbidopa. Additionally, long-term studies have shown sustained motor and quality-of-life benefits over 12 months, despite the challenges of infusion-site reactions. Importantly, the side-effect profile of foslevodopa-foscarbidopa is manageable, with most adverse events being mild to moderate. 

From a clinical perspective, foslevodopa-foscarbidopa represents a viable alternative to other CDS options such as continuous apomorphine infusion or levodopa-carbidopa intestinal gel. Its minimally invasive administration via a portable subcutaneous pump offers enhanced patient autonomy and feasibility for daily use. However, careful patient selection, education, and monitoring are essential to optimize outcomes and manage potential infusion-site complications. 

Our review emphasizes the potential of foslevodopa-foscarbidopa to transform the therapeutic landscape of advanced PD. While promising, challenges remain regarding long-term safety, cost-effectiveness, and integration into clinical practice. Further research is needed to explore its comparative efficacy against established therapies and its impact on non-motor symptoms and patient quality of life. 

In summary, foslevodopa-foscarbidopa offers a novel and effective approach for managing advanced PD, addressing critical unmet needs in the current treatment paradigm. Its development underscores the importance of innovation in achieving continuous dopaminergic stimulation and improving outcomes for patients with advanced PD. 

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Young Researcher Highlights are selected monthly by the Steering Committee of the Young Members Group

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