Clinical GDNF delivery methods for Parkinson's disease

Area of Science:

• Neuroscience
• Biomedical Engineering
• Gene Therapy

Background:

• Intracerebral glial cell line-derived neurotrophic factor (GDNF) delivery is a promising therapeutic strategy for Parkinson's disease (PD).
• Previous clinical trials using GDNF protein have yielded inconclusive results, necessitating advancements in delivery methods.
• A new sham-surgery controlled trial for GDNF gene therapy began in 2024, highlighting the ongoing evolution of PD treatments.

Purpose of the Study:

• To provide an updated review of intracerebral delivery methods for GDNF protein and gene therapy in PD clinical trials.
• To emphasize the critical role of delivery techniques in interpreting trial results and future prospects.
• To compare and contrast GDNF protein infusion versus gene therapy strategies, addressing challenges in targeting the putamen.

Main Methods:

• Review of current literature and clinical trial data on intracerebral GDNF delivery for PD.
• Comparison of convection-enhanced delivery (CED) for protein and gene therapy administration.
• Discussion of anatomical and physiological challenges in achieving optimal therapeutic coverage of the putamen.

Main Results:

• Convection-enhanced delivery (CED) is widely considered the optimal strategy for localized intracerebral therapeutic administration.
• Debate continues regarding the necessity of co-infusion with gadolinium contrast agents and intraoperative MRI (iMRI) for visualizing distribution.
• Well-designed trials with clear results are crucial for advancing GDNF-based therapies for PD.

Conclusions:

• Optimizing intracerebral delivery methods is paramount for the success of GDNF-based therapies in Parkinson's disease.
• Understanding the nuances of delivery techniques, such as CED, is essential for evaluating current and future clinical trial outcomes.
• Further research and well-designed trials are needed to fully elucidate the potential of GDNF in treating PD.