Phase II trial of intravenous human dental pulp stem cell therapy for Huntington's disease: a randomized, double-blind, placebo-controlled study.

BACKGROUND

Huntington's disease (HD) is a rare, autosomal dominant neurodegenerative disorder caused by an expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin (HTT) gene. It manifests with motor, cognitive, and behavioural impairments, leading to progressive functional decline over approximately 20 years. Despite symptomatic treatments, no approved disease-modifying therapies are currently available, though experimental approaches are under investigation. Recent research has explored human dental pulp stem cells (hDPSCs) as a potential therapeutic approach due to their neurotrophic properties and ability to modulate neuroinflammation. This Phase II trial aimed to evaluate the safety and efficacy of NestaCell®, an allogeneic hDPSC-based therapy, in patients with HD.

METHODS

This randomised, double-blind, placebo-controlled trial included 35 patients assigned at a 2:2:1 ratio to receive hDPSCs at 1 million cells/kg, 2 million cells/kg, or placebo over nine intravenous infusions across 11 months. The primary endpoint was the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score (TMS) change. Secondary outcomes included UHDRS Total Functional Capacity (TFC), Total Chorea Score (TCS), Functional Checklist (FC), and magnetic resonance imaging (MRI) based white matter quantification. Safety was assessed by monitoring treatment-emergent adverse events (TEAEs) and laboratory parameters.

RESULTS

Both doses demonstrated a favourable safety profile, with no increased incidence of adverse events compared to the placebo. No serious adverse event was deemed related to treatment. Both doses significantly improved UHDRS-TMS compared to placebo (p = 0.005), while the 2 million cells/kg group showed significant benefits in UHDRS-TFC (p = 0.011). Additional improvements were observed in the TCS and FC, suggesting a broader clinical impact. MRI analysis indicated a non-significant trend toward neuroprotection, with slower central nervous system (CNS) white and grey matter decline in treated patients.

CONCLUSIONS

NestaCell® was well tolerated and showed statistically significant improvements in motor and functional outcomes in HD patients. While MRI trends suggest a potential neuroprotective effect, further investigation is warranted. These findings support the advancement to a Phase III trial to confirm efficacy and long-term safety in a larger cohort.

TRIAL REGISTRATION

This study was registered on August 16, 2017, at ClinicalTrials.gov (identifier: NCT03252535; https://clinicaltrials.gov/search?cond=NCT03252535 ).