592 - Autologous Stem Cells from Human Exfoliated Deciduous Teeth (SHED) in Children with Cerebral Palsy: A First-in-Human Phase I Trial (Interim Analysis)

Publication Number: 3573.592

Takahiro Kanzawa, Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Aichi, Japan; Fumie Kinoshita, Nagoya University Hospital, Nagoya, Aichi, Japan; Toshihiko Suzuki, Nagoya University Hospital,, Nagoya, Aichi, Japan; Ryosuke Miura, Nagoya University Hospital, Nagoya, Aichi, Japan; Ryuichi Tanaka, Nagoya University Hospital, Nisshin-shi, Aichi, Japan; Akinobu Taniguchi, Center for Maternal-Neonatal Care, Division of Neonatology, Nagoya University Hospital, Nagoya, Aichi, Japan; Kazuto Ueda, Nagoya University, Nagoya, Aichi, Japan; Yukako Muramatsu, Nagoya university hospital, Nagoya, Aichi, Japan; Tomohiro Mori, Nagoya University Hospital, Nagoya, Aichi, Japan; Yuki Fugane, Nagoya University Hospital, nagoya, Aichi, Japan; Kiyoshi Sakai, Nagoya University, Nagoya, Aichi, Japan; Hideharu Hibi, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Sho Narahara, Aichi Prefecture Mikawa Aoitori Medical and Rehabilitation Center for Developmental Disabilities, Okazaki, Aichi, Japan; Hiroyuki Kidokoro, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Jun Natsume, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Shinichi Kishi, Aichi University of Education, Nagoya, Aichi, Japan; Shinobu Shimizu, Nagoya University Hospital, Nagoya, Aichi, Japan; Yoshiaki Sato, Nagoya University Hospital, Nagoya, Aichi, Japan; Takashi Maeda, Nagoya university Hospital, Nagoya, Aichi, Japan

Background: Cerebral palsy (CP), often caused by perinatal hypoxic-ischemic encephalopathy (HIE), remains a significant cause of lifelong neurological disability and lacks curative treatments. While some stem cell therapies have been explored, none have progressed to Phase clinical III trials, highlighting an urgent unmet medical need. Stem cells from human exfoliated deciduous teeth (SHED), originating from the neural crest, offer a promising alternative. Preclinical studies demonstrate their strong neurogenic and neuroprotective potential via paracrine mechanisms, improving motor function in chronic-phase CP models and showing superior neurogenic effects compared to other mesenchymal stromal cells.

Objective: This first-in-human, open-label Phase I clinical trial registered with jRCTb040230042, aimed to evaluate the safety, tolerability, feasibility, and preliminary efficacy of intravenous administration of autologous SHED in children with CP. Efficacy assessments are planned up to 52 weeks post-infusion; this report presents the interim findings at 12 weeks.

Design/Methods: Three children aged 6-11 years with CP (Gross Motor Function Classification System [GMFCS] Level III) secondary with perinatal HIE were enrolled. Each participant received a single intravenous infusion of autologous SHED at a target dose of 3 × 10⁶ cells/kg. The primary outcome was safety, assessed by the incidence of adverse events within 4 weeks post-infusion. Exploratory efficacy outcomes, including Gross Motor Function Measure-66 (GMFM-66) and muscle tone (Modified Ashworth Scale), were evaluated at 12 weeks.

Results: All three patients completed the SHED infusion without any acute infusion-related adverse reactions. No serious adverse events related to SHED administration were observed during the 4-week follow-up period. At 12 weeks post-infusion, GMFM-66 scores improved in all patients, with an average increase of 3.2 points, exceeding the minimal clinically important difference. In addition, knee flexion tone, assessed using the Modified Ashworth Scale, showed an improvement of 0.5 to 2 grades. The GMFM evolution ratio (GMFMER), which indicates improvement relative to natural progression, was markedly high, with a mean value of 40.5.

Conclusion(s): This interim analysis demonstrates that intravenous administration of autologous SHED is safe, tolerable, and feasible for children with CP. The preliminary data suggest clinically meaningful motor function improvement. The upcoming 52-week results are expected to further substantiate these findings, supporting the need for further investigation in larger, controlled clinical trials.

Schematic overview of the phase I clinical trial
This figure illustrates the study design and timeline. It outlines the key stages of the trial, including patient screening and enrollment, extraction of deciduous teeth, isolation and expansion of autologous SHED, single intravenous administration of SHED, and the schedule for safety and efficacy assessments post-infusion.


Changes in blood test results before and after SHED infusion.


Improvement in Gross Motor Function (GMFM-66) at 12 weeks after SHED infusion
Gross Motor Function Measure-66 (GMFM-66) scores for all three participants at baseline (Pre) and 12 weeks post-infusion. All patients showed an improvement in their GMFM-66 scores. The average increase was 3.2 points, which is considered a clinically meaningful improvement.