A phase I, open-label study of intravenous human dental pulp stem cells (NestaCell®) at two dose levels in patients with Huntington's disease.

backgroundHuntington's disease (HD) is a progressive neurodegenerative disorder with no approved disease-modifying therapies. Human dental pulp stem cells (hDPSCs) offer potential therapeutic benefits due to their neurogenic, neurotrophic, and immunomodulatory properties. This prospective, open-label, single-centre, first-in-human clinical trial evaluated the safety, tolerability, and preliminary efficacy of intravenous hDPSC in patients with HD.

methodsSix male patients with HD received intravenous infusions of hDPSCs in two dosage cohorts: three patients received 1 million cells/kg, and three received 2 million cells/kg. The treatment protocol consisted of cycles of three infusions at monthly intervals followed by subsequent administration cycles every six months, as per a protocol amendment based on the initial favourable safety outcomes. The total number of infusions ranged from 4 to 26 over the five years. During the first year, all patients underwent intensive multiparametric monitoring in an intensive care unit (ICU) for 48 h after each infusion.

resultsNo adverse events occurred during the 48-h ICU monitoring or within 15 days post-infusion. Of 41 treatment-emergent adverse events (TEAEs) reported during follow-up, 35 were judged unrelated to the hDPSCs, mainly reflecting disease progression or incidental findings. Six treatment-emergent adverse events (TEAEs) were considered treatment-related, involving transient changes in hair pigmentation or regrowth. One patient discontinued due to a serious adverse event-lung cancer arising from a pre-existing pulmonary nodule identified at enrolment. Genetic analysis of the excised tumour showed no evidence of investigational product engraftment, supporting its non-tumorigenic nature. The same patient experienced a severe depressive episode lasting approximately 93 days; the relationship to treatment was considered uncertain. Minor, clinically insignificant fluctuations in CD4/CD8 lymphocyte counts and cytokine levels were observed. Preliminary efficacy analyses indicated potential stabilisation of disease progression, particularly in the Unified Huntington's Disease Rating Scale (UHDRS), Total Motor Score (TMS) and Total Functional Capacity (TFC).

conclusionshDPSCs infusions were well tolerated and exhibited a favourable safety profile, even with prolonged exposure and follow-up. These findings support the continued clinical development and warrant further investigation in more extensive trials to assess therapeutic efficacy in Huntington's disease.

trial registrationThis study was registered on April 4, 2016, at ClinicalTrials.gov (identifier: NCT02728115; https://clinicaltrials.gov/study/NCT02728115 ).