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Background <p>Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition of etiology, characterized by deficits in social communication and restricted, repetitive behaviors. Despite its growing prevalence, no treatment has yet demonstrated consistent efficacy across the full spectrum of ASD phenotypes. This Phase I, open-label study investigates the safety and feasibility of three repeated intrathecal injections of allogeneic Umbilical Cord Tissue–Derived Mesenchymal Stromal Cells (UC-MSCs) in children diagnosed with ASD.</p> Methods <p>Five children (aged 3-7) with ASD, confirmed by Diagnostic and Statistical Manual of Mental Disorders- Fifth Edition (DSM-5) criteria and on stable behavioral and pharmacologic regimens for at least two months, received three intrathecal (IT) injections of 20 × 10⁶ UC-MSCs at one-month intervals. Safety was monitored over six months based on Common Terminology Criteria for Adverse Events (CTCAE). Preliminary behavioral assessments, including the Childhood Autism Rating Scale (CARS), Autism Treatment Evaluation Checklist (ATEC), and the Behavior Problem Inventory (BPI-S), were conducted at the baseline, one-, two-, four-, and six-month follow-ups. Cerebrospinal fluid (CSF) cytokine profiles were measured prior to each injection. Electroencephalography (EEG) and Diffusion Tensor Imaging (DTI) were performed at baseline and the final follow-up.</p> Results <p>The treatment was safe and well-tolerated with no serious adverse events (SAEs). All participants experienced at least one mild to moderate, transient adverse event (AEs), most commonly fever (5/5) and nausea (4/5). Exploratory behavioral improvements were observed in CARS in all children, while two participants moved from the mild-to-moderate to the non-autistic ranges, and three shifted from the severe to the mild-to-moderate range. Other measures also improved, though the persistence of these improvements was varied. CSF cytokines showed consistent reduction, particularly in TNF-<InlineEquation ID="IEq1"><EquationSource Format="TEX">\(\:\alpha\:\)</EquationSource></InlineEquation> and IL-6 levels across participants, confirming the immunomodulatory impact of UC-MSC administration. The EEG findings revealed that the spectral pattern shifted toward a more typical profile in one participant after treatment.</p> Conclusions <p>This Phase I study showed that three repeated IT injections of UC-MSCs are safe and well-tolerated in children with ASD. Preliminary behavioral and biomarker improvements warrant further study in larger controlled trials.</p> Trial registration <p>Trial Registration ID: IRCT20200217046526N3.</p>

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Three repeated intrathecal injections of allogenic umbilical cord-derived mesenchymal stromal cells in autism spectrum disorder: a Phase I clinical trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月30日

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  • Elaheh Khodadoust,
  • Hadi Zarafshan,
  • Masoumeh Nouri,
  • Anahita Majmaa,
  • Ali Khaleghi,
  • Fatemeh Zamani,
  • Milad Seyfi,
  • Mohammad Amin Shahrbaf,
  • Solaleh Samimi,
  • Bahareh Sadri,
  • Seyedeh Malihe Mahmoodi,
  • Norouz Abdi,
  • Ali Ghasemi,
  • Mahmoud Reza Ashrafi,
  • Morteza Zarrabi,
  • Massoud Vosough,
  • Mohammad Reza Mohammadi

摘要

Background

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition of etiology, characterized by deficits in social communication and restricted, repetitive behaviors. Despite its growing prevalence, no treatment has yet demonstrated consistent efficacy across the full spectrum of ASD phenotypes. This Phase I, open-label study investigates the safety and feasibility of three repeated intrathecal injections of allogeneic Umbilical Cord Tissue–Derived Mesenchymal Stromal Cells (UC-MSCs) in children diagnosed with ASD.

Methods

Five children (aged 3-7) with ASD, confirmed by Diagnostic and Statistical Manual of Mental Disorders- Fifth Edition (DSM-5) criteria and on stable behavioral and pharmacologic regimens for at least two months, received three intrathecal (IT) injections of 20 × 10⁶ UC-MSCs at one-month intervals. Safety was monitored over six months based on Common Terminology Criteria for Adverse Events (CTCAE). Preliminary behavioral assessments, including the Childhood Autism Rating Scale (CARS), Autism Treatment Evaluation Checklist (ATEC), and the Behavior Problem Inventory (BPI-S), were conducted at the baseline, one-, two-, four-, and six-month follow-ups. Cerebrospinal fluid (CSF) cytokine profiles were measured prior to each injection. Electroencephalography (EEG) and Diffusion Tensor Imaging (DTI) were performed at baseline and the final follow-up.

Results

The treatment was safe and well-tolerated with no serious adverse events (SAEs). All participants experienced at least one mild to moderate, transient adverse event (AEs), most commonly fever (5/5) and nausea (4/5). Exploratory behavioral improvements were observed in CARS in all children, while two participants moved from the mild-to-moderate to the non-autistic ranges, and three shifted from the severe to the mild-to-moderate range. Other measures also improved, though the persistence of these improvements was varied. CSF cytokines showed consistent reduction, particularly in TNF-\(\:\alpha\:\) and IL-6 levels across participants, confirming the immunomodulatory impact of UC-MSC administration. The EEG findings revealed that the spectral pattern shifted toward a more typical profile in one participant after treatment.

Conclusions

This Phase I study showed that three repeated IT injections of UC-MSCs are safe and well-tolerated in children with ASD. Preliminary behavioral and biomarker improvements warrant further study in larger controlled trials.

Trial registration

Trial Registration ID: IRCT20200217046526N3.