Safety and tolerability of a Muse cell-based product in neonatal hypoxic-ischemic encephalopathy with therapeutic hypothermia (SHIELD trial)

Hypoxic-ischemic encephalopathy (HIE), associated with high mortality and neurological sequelae, lacks established treatment except therapeutic hypothermia. Clinical-grade multilineage-differentiating stress-enduring (Muse) cells (CL2020) demonstrated safety and efficacy in nonclinical HIE rat models, thereby leading to an investigator-initiated clinical trial to evaluate CL2020 safety and tolerability in neonatal HIE as a single-center open-label dose-escalation study with 9 neonates with moderate-to-severe HIE who received therapeutic hypothermia. Each patient received a single intravenous injection of CL2020 cells between 5 and 14 days of age. The low-dose (3 patients) and high-dose (6 patients) groups received 1.5 × 106 and 1.5 × 107 cells/dose, respectively. The occurrence of any adverse event within 12 weeks following CL2020 administration was the primary endpoint of this trial. No significant changes in physiological signs including heart rate, blood pressure, and oxygen saturation were observed during or after administration. The only adverse event that may be related to cell administration was a mild γ-glutamyltransferase level elevation in one neonate, which spontaneously resolved without any treatment. All patients enrolled in the trial survived, and normal developmental quotients (≥ 85) in all 3 domains of the Kyoto Scale of Psychological Development 2001 were observed in 67% of the patients in this trial. CL2020 administration was demonstrated to be safe and tolerable for neonates with HIE. Considering the small number of patients, a randomized controlled confirmatory study is warranted to verify these preliminary findings and evaluate the efficacy of this therapy.

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Publication Details

Journal
Stem Cells Translational Medicine
Published
2024-10-14
DOI
https://doi.org/10.1093/stcltm/szae071
Citations
11
Primary Topic
Neonatal and fetal brain pathology
Type
article
Field-Weighted Citation Impact
12.20
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article

Safety and tolerability of a Muse cell-based product in neonatal hypoxic-ischemic encephalopathy with therapeutic hypothermia (SHIELD trial)

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Neonatal and fetal brain pathology
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article

Safety and tolerability of a Muse cell-based product in neonatal hypoxic-ischemic encephalopathy with therapeutic hypothermia (SHIELD trial)

Shinobu Shimizu, Yuichiro Sugiyama, Yoshihiro Tanahashi, Toshihiko Suzuki, Takeshi Sahashi, Taihei Tanaka, A. Kotani, Masatoshi Yoshikane, Hiromasa Uchizono, Akiko Saito, Kentaro Ueda, Seiji Hayashi, Yuichi Kato, Ryuichi Tanaka, Yukihiro Suetake, Kazuto Ueda, Toshimichi Yamamoto, Akinobu Taniguchi, Sakiko Suzuki, Yue Xu, Yasuyuki Fujita, Akemi Katayama, Hisako Matsui‐Hirai, Osuke Iwata, Naoko Hayashi, R. Goto, Nao Matsuyama, Yasuko Watarai, Miharu Ito, Ryosuke Miura, Fumie Kinoshita, Masahiko Ando, Yumiko Kobayashi, Kennosuke Tsuda, Hiroyuki Kidokoro, Aiko Aoyama, Tomoshige Tanimura, Gaku SHOJI, Chikashi Nishimura, Azuma Ikari, Yoshiaki Sato, Akihiro Hirakawa, Masahiro Hayakawa, Yuki Hashimoto, Yukako Muramatsu, Tetsuo Hattori, Kanji Muramatsu, Makoto Oshiro, Takahiro Kanzawa, Koya Kawase, Masaaki Mizuno
article en
11 citations

Abstract

Hypoxic-ischemic encephalopathy (HIE), associated with high mortality and neurological sequelae, lacks established treatment except therapeutic hypothermia. Clinical-grade multilineage-differentiating stress-enduring (Muse) cells (CL2020) demonstrated safety and efficacy in nonclinical HIE rat models, thereby leading to an investigator-initiated clinical trial to evaluate CL2020 safety and tolerability in neonatal HIE as a single-center open-label dose-escalation study with 9 neonates with moderate-to-severe HIE who received therapeutic hypothermia. Each patient received a single intravenous injection of CL2020 cells between 5 and 14 days of age. The low-dose (3 patients) and high-dose (6 patients) groups received 1.5 × 106 and 1.5 × 107 cells/dose, respectively. The occurrence of any adverse event within 12 weeks following CL2020 administration was the primary endpoint of this trial. No significant changes in physiological signs including heart rate, blood pressure, and oxygen saturation were observed during or after administration. The only adverse event that may be related to cell administration was a mild γ-glutamyltransferase level elevation in one neonate, which spontaneously resolved without any treatment. All patients enrolled in the trial survived, and normal developmental quotients (≥ 85) in all 3 domains of the Kyoto Scale of Psychological Development 2001 were observed in 67% of the patients in this trial. CL2020 administration was demonstrated to be safe and tolerable for neonates with HIE. Considering the small number of patients, a randomized controlled confirmatory study is warranted to verify these preliminary findings and evaluate the efficacy of this therapy.

Stem Cells Translational MedicineVol. 13(11)
Tokyo Medical and Dental University (JP), Nagoya City University (JP), Nagoya University Hospital (JP), Ichinomiya Municipal City Hospital (JP), Okazaki City Hospital (JP), Japanese Red Cross Nagoya Daiichi Hospital (JP), Mie Chuo Medical Center (JP), Anjo Kosei Hospital (JP), Toyohashi Municipal Hospital (JP), Nagoya Medical Center (JP), Japanese Red Cross Nagoya Daini Hospital (JP), Nagoya University (JP)
Good health and well-being
Openalex Percentile: Top 1%
Neonatal and fetal brain pathology
12.20
DOIOpen Access PDFOpenAlex
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