Key Takeaways & Executive Findings
- •• First-in-human trial demonstrates that intravenous hDPSCs (NestaCell®) are safe and well-tolerated in Huntington’s disease patients over five years. • No serious adverse events were directly attributed to the stem cell product; the only serious event (lung cancer) was unrelated to the cells, with no evidence of engraftment. • Treatment-related adverse events were limited to transient hair pigmentation changes, indicating a favorable safety profile. • The study supports further clinical development of hDPSC therapy for neurodegenerative disorders, with preliminary evidence of potential efficacy.
Abstract
Background Huntington’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. Methods Six 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. Results No 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
1. Introduction
Human dental pulp stem cells (hDPSCs) represent a promising resource for cell-based therapies due to their multipotency, immunomodulatory capabilities, and ease of isolation [1–4]. Comparative analyses between hDPSCs and other mesenchymal stem cell (MSC) sources, such as those derived from umbilical cord and menstrual blood, suggest that hDPSCs exhibit distinct advantages in terms of proliferation rates, differentiation potential, and accessibility [3, 5].
Numerous studies have demonstrated the potential of hDPSCs in regenerative medicine, particularly in neurological applications, due to their neurogenic and neurotrophic properties [4, 6–11]. hDPSCs have demonstrated efficacy in animal models for spinal cord injury [12, 13], stroke-related chronic disabilities [9], Parkinson’s disease [14, 15], retinal degeneration [6, 16], osteoarthritis [17, 18], wound healing and muscle regeneration [19], bone regeneration and repair [20], and neurodegenerative disorders [4, 8, 21]. These beneficial effects are primarily attributed to the secretion of neural growth factors and cytokines that modulate inflammation, promote tissue regeneration, and support neuronal survival and repair [22–25]. Additionally, their regenerative and immunomodulatory properties have sparked interest in their potential therapeutic use in treating COVID-19 [25].
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Joyce Macedo Sanches Fernandes, Eduardo Pagani, Cristiane Valverde Wenceslau, Leandro Hideki Ynoue, Luciana Ferrara, Irina Kerkis (2026). A phase I, open-label study of intravenous human dental pulp stem cells (NestaCell®) at two dose levels in patients with Huntington’s disease. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-025-04703-w
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Frequently Asked Questions
What is the safety profile of intravenous human dental pulp stem cells in Huntington's disease patients?
The phase I trial reported no adverse events during ICU monitoring or within 15 days post-infusion. Of 41 TEAEs, only six were treatment-related, involving transient hair pigmentation changes. One serious adverse event (lung cancer) was unrelated to the cells, with no evidence of engraftment.
How were the stem cells administered in this study?
Patients received intravenous infusions of hDPSCs (NestaCell®) in two dosage cohorts: 1 million cells/kg or 2 million cells/kg. The protocol involved cycles of three infusions at monthly intervals, followed by maintenance cycles every six months, with total infusions ranging from 4 to 26 over five years.
What is NestaCell®?
NestaCell® is a novel product consisting of cryopreserved human dental pulp stem cells suspended in sterile saline. It expresses nestin and secretes high levels of brain-derived neurotrophic factor (BDNF), which are important for neuronal support.
What were the key findings regarding efficacy?
The study primarily assessed safety and tolerability. Preliminary efficacy outcomes were not detailed in the abstract, but the favorable safety profile and lack of serious adverse events support further investigation into potential therapeutic benefits.
What is the significance of this trial for Huntington's disease treatment?
This first-in-human trial provides critical safety data for hDPSC therapy in HD, a condition with no disease-modifying treatments. The results pave the way for larger efficacy trials and offer hope for a novel cell-based approach.
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