A PHASE I CLINICAL TRIAL ON INTRAVENOUS ADMINISTRATION OF IMMATURE HUMAN DENTAL PULP STEM CELLS (NESTACELL HDTM) TO HUNTINGTON'S DISEASE PATIENTS

Abstract

<h3>Background</h3> Huntington′s disease (HD) is a neurodegenerative condition caused by an increase in the CAG repeats of the huntingtin (HTT) gene at chromosome 4. It is a rare disease; whose prevalence varies from 0.4 to 5.7 cases per 100,000 habitants. The clinical manifestations usually start by the fourth decade of age with motor, cognitive and behavioral features, that typically evolve for 10 to 20 years until death. Currently, there is no curative treatment. Nestacell HD is an allogeneic cell therapy manufactured from the human immature dental pulp stem cells by the Brazilian company Cellavita. This study aimed at assessing the safety, tolerability, and preliminary data on the efficacy of intravenous injections of Nestacell HD. It was approved by the local IRB, CONEP, and ANVISA. <h3>Methods</h3> This is a first-in-human, uncontrolled, open-label, Phase I clinical trial with six HD participants. The study started following the patients for 4 months to collect baseline data. Then, they received 3 administrations with a 1-month interval of either 1 million cells per Kg (first 3 patients) or 2 million cells per kg (last 3 patients) by the intravenous route. The patients were then followed for 2 years. The safety was evaluated based on the adverse events (AV) incidence, severity, and causality. The efficacy was evaluated using the Unified Huntington‘s Disease Rating Scale – UHDRS. The immunological response was evaluated by CD4+ and CD8+ proliferation, and inflammatory markers (cytokines). <h3>Results</h3> All participants completed the treatment and the two-year follow-up period. The treatment was well tolerated. There were no treatment-related serious adverse events (SAE), nor any AE led to dropout. No patient increased the cytokines or the CD4/CD8. Five patients had improvement to the UHDRS motor domain, which started two weeks after the first administration and remained for six to nine months after the last administration. All patients were entitled to additional infusions to maintain clinical improvement. <h3>Conclusion</h3> The treatment with Nestacell HD was well tolerated and might have improved the HD motor manifestations; thus justifying further Phase 2 clinical trials.