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. 2024 Nov 12;13(11):1053-1066.
doi: 10.1093/stcltm/szae071.

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

Collaborators, Affiliations

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

Yoshiaki Sato et al. Stem Cells Transl Med. .

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.

Keywords: Muse; cerebral palsy; hypothermia; hypoxic–ischemic encephalopathy; mesenchymal stem cell; neonates.

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Conflict of interest statement

Y.S. and S.Sh. had collaborative projects with research funding from LSII for perinatal diseases. S.Sh. and A.H. received fees based on a consultation contract from LSII. Y.S., S.S., T.S., and M.H. have a patent for the application of Muse cells in the treatment of HIE and other indications. LSII provided CL2020 for this clinical trial free of charge. The LSII was not involved in the design, conduct, or analysis of the results.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Study framework. The study used a 3 + 3 design, and the schematic diagram illustrates the framework of this clinical trial. It provides an overview of the enrolment schedule, the timing of CL2020 cell administration, as well as the assessments and visits for each patient. Additionally, it indicates when the Data Safety Monitoring Board (DSMB) meetings transpired. The DSMB convened for safety evaluation 4 weeks following CL2020 cell administration to the first patient in each cohort and 12 weeks following administration to the third patient in each cohort. The meetings aimed to determine if it was appropriate to proceed with enrolling the remaining participants on the basis of the safety data and evaluation.
Figure 2.
Figure 2.
Physiological signs and SpO2. a) Heart rate, b) blood pressure, c) SpO2, d) Body temperature. These parameters are recorded before and immediately; at 1 hour; at 1, 3, and 7 days; and at 2, 4, 12, 26, 38, 52, and 78 weeks after CL2020 administration.

References

    1. Kurinczuk JJ, White-Koning M, Badawi N.. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy [Research Support, Non-U.S. Gov’t]. Early Hum Dev. 2010;86(6):329-338. 10.1016/j.earlhumdev.2010.05.010 - DOI - PubMed
    1. Graham EM, Ruis KA, Hartman AL, Northington FJ, Fox HE.. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol. 2008;199(6):587-595. 10.1016/j.ajog.2008.06.094 - DOI - PubMed
    1. Reid SM, Meehan E, McIntyre S, et al.; Australian Cerebral Palsy Register Group. Temporal trends in cerebral palsy by impairment severity and birth gestation. Dev Med Child Neurol. 2016;58(Suppl 2):25-35. 10.1111/dmcn.13001s - DOI - PubMed
    1. Centers for Disease Control and Prevention (CDC). Economic costs associated with mental retardation, cerebral palsy, hearing loss, and vision impairment--United States, 2003. MMWR Morb Mortal Wkly Rep. 2004;53(3):57-59. - PubMed
    1. Gluckman PD, Wyatt JS, Azzopardi D, et al.. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy. Lancet. 2005;365(9460):663-670. 10.1016/S0140-6736(05)17946-X - DOI - PubMed