Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles:a case report

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外文摘要：Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient's Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54 × 1012(×2),and then consecutive infusions of 7.5 × 1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco's phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.

外文关键词：

allogeneicamyotrophic lateral sclerosisexosomesinfusionneuromuscular junctionSchwann cell

作者：

Pascal J.Goldschmidt-Clermont、Aisha Khan、George Jimsheleishvili、Patricia Graham、Adriana Brooks、Risset Silvera、Alexander J.P.Goldschmidt、Damien D.Pearse、W.Dalton Dietrich、Allan D.Levi、James D.Guest

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作者单位：

Miller School of Medicine,University of Miami,Miami,FL,USA

Stem Cell Institute,Miller School of Medicine,University of Miami,Miami,FL,USA

The Miami Project to Cure Paralysis,Miller School of Medicine,University of Miami,Miami,FL,USA

Alzady International LLC,Miami,FL,USA

Neurological Surgery,Miller School of Medicine,University of Miami,Miami,FL,USA

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出版年：

2025

DOI：

10.4103/NRR.NRR-D-23-01815

中国神经再生研究(英文版)

中国康复医学会

中国神经再生研究(英文版)

影响因子：0.902

ISSN：1673-5374

年,卷(期)：2025.20(4)