Title: Deferiprone in Parkinson’s Disease: Motor, Imaging, and Safety Outcomes Across Randomized Trials
Authors: Jamir Pitton Rissardo, Ana Leticia Fornari Caprara
Conference: 2026 ANA Annual Meeting, San Diego, CA
BACKGROUND/OBJECTIVE
Iron accumulation in the substantia nigra (SN) contributes to oxidative injury and neurodegeneration in Parkinson’s disease (PD). Deferiprone (DFP), a brain‑penetrant iron chelator, has been evaluated as a potential disease‑modifying therapy, with inconsistent trial‑level results. We conducted a systematic review and meta‑analysis of randomized controlled trials (RCTs) to quantify the effects of DFP on motor outcomes, neuroimaging biomarkers, and safety in PD.
DESIGN/METHODS
Pubmed and ClinicalTrials.gov were searched for RCTs comparing DFP versus placebo in PD. Random‑effects meta‑analyses (REML estimator) were performed. Outcomes assessed were motor (MDS‑UPDRS Part III), MRI iron measures (SN, caudate, and putamen), serum ferritin, cognition, (MoCA/MMSE), quality-of-life (PDQ‑39), and adverse events. Effect sizes were expressed as standardized mean differences (SMD) or mean differences (MD). Heterogeneity was quantified using I2.
RESULTS
Four RCTs (n = 474 participants) were included. Pooled analysis demonstrated no significant improvement in motor symptoms with DFP versus placebo (SMD −0.11, 95% CI −0.43 to 0.21; p = 0.51; I2 = 0%). Dose‑stratified 9‑month analyses showed no significant effect across 300–1200 mg/day (MD 0.30, 95% CI −1.93 to 2.52; I2 = 64%). MRI iron outcomes showed no significant pooled effect in the SN (SMD 0.20, 95% CI −0.78 to 1.19; I2 = 79%), caudate (SMD −0.05, 95% CI −1.20 to 1.11), or putamen (SMD 0.01, 95% CI −0.95 to 0.96). DFP significantly reduced serum ferritin (MD −45.4 ng/mL, 95% CI −78.0 to −12.9; p = 0.006; I2 = 0%). No significant between‑group difference were observed for quality-of-life (MD 1.04, 95% CI −3.26 to 5.33) and cognition (SMD −0.10, 95% CI −0.48 to 0.28; p = 0.62). Risk of any adverse event was higher with DFP (RR 1.49, 95% CI 1.23–1.81; p < 0.001), with a non‑significant increase in serious adverse events and hematologic toxicity.
CONCLUSIONS
Across randomized evidence, deferiprone does not improve motor, cognitive, or quality‑of‑life outcomes in PD despite demonstrable iron chelation. Increased adverse events and lack of clinical efficacy do not support routine use of DFP as symptomatic or disease‑modifying therapy in PD.
Citation
Rissardo JP, Caprara AL. Deferiprone in Parkinson’s Disease: Motor, Imaging, and Safety Outcomes Across Randomized Trials. Ann Neurol 2026;100(Suppl 37):S311.