Extracellular vesicle-based therapy for amyotrophic lateral sclerosis

Sadanandan, Nadia; Lee, Jea-Young; Garbuzova‐Davis, Svitlana

doi:10.4103/bc.bc_9_21

Cited by 13 publications

(13 citation statements)

References 61 publications

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“…Human BM-MSC-derived EVs have further demonstrated their capacity to induce differentiation in neural progenitor cells and have yielded beneficial outcomes in PD animal models, enhancing both motor function and histological integrity [66]. Additionally, EPC-derived EVs have been documented to interface with brain endothelial cells, promoting the restoration of the compromised blood-CNS barrier in ALS models [67,68].…”

Section: Osteo-neural Crosstalk: Evs From Bone Marrow Stem Cellsmentioning

confidence: 99%

Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles

Liu,

Shen,

Wan

et al. 2024

J Nanobiotechnol

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Neurodegenerative diseases (NDDs) such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis epitomize a class of insidious and relentless neurological conditions that are difficult to cure. Conventional therapeutic regimens often fail due to the late onset of symptoms, which occurs well after irreversible neurodegeneration has begun. The integrity of the blood-brain barrier (BBB) further impedes efficacious drug delivery to the central nervous system, presenting a formidable challenge in the pharmacological treatment of NDDs. Recent scientific inquiries have shifted focus toward the peripheral biological systems, investigating their influence on central neuropathology through the lens of extracellular vesicles (EVs). These vesicles, distinguished by their ability to breach the BBB, are emerging as dual operatives in the context of NDDs, both as conveyors of pathogenic entities and as prospective vectors for therapeutic agents. This review critically summarizes the burgeoning evidence on the role of extracerebral EVs, particularly those originating from bone, adipose tissue, and gut microbiota, in modulating brain pathophysiology. It underscores the duplicity potential of peripheral EVs as modulators of disease progression and suggests their potential as novel vehicles for targeted therapeutic delivery, positing a transformative impact on the future landscape of NDD treatment strategies.Search strategy A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus from January 2000 to December 2023. The search combined the following terms using Boolean operators: “neurodegenerative disease” OR “Alzheimer’s disease” OR “Parkinson’s disease” OR “Amyotrophic lateral sclerosis” AND “extracellular vesicles” OR “exosomes” OR “outer membrane vesicles” AND “drug delivery systems” AND “blood-brain barrier”. MeSH terms were employed when searching PubMed to refine the results. Studies were included if they were published in English, involved human subjects, and focused on the peripheral origins of EVs, specifically from bone, adipose tissue, and gut microbiota, and their association with related diseases such as osteoporosis, metabolic syndrome, and gut dysbiosis. Articles were excluded if they did not address the role of EVs in the context of NDDs or did not discuss therapeutic applications. The titles and abstracts of retrieved articles were screened using a dual-review process to ensure relevance and accuracy. The reference lists of selected articles were also examined to identify additional relevant studies.

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Section: Osteo-neural Crosstalk: Evs From Bone Marrow Stem Cellsmentioning

confidence: 99%

Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles

Liu,

Shen,

Wan

et al. 2024

J Nanobiotechnol

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“…Experimental application of hBM mesenchymal stroma, endothelial or muscle progenitor cells further increased VEGF expression, suggesting to combine the advantages of cell-based and exerkine approaches (reviewed in [ 158 ]). Intriguingly, endothelial progenitor cells additionally release beneficial EVs, to strengthen and repair the microvascular wall in experimental ALS [ 159 ].…”

Section: Targeting Brain Vascular Health To Preserve Microvascular In...mentioning

confidence: 99%

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Schreiber

Bernal

Ulbrich

et al. 2023

Cells

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Brain vascular health appears to be critical for preventing the development of amyotrophic lateral sclerosis (ALS) and slowing its progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in their small cerebral blood vessels. Impaired vascular brain health has detrimental effects on motor neurons: vascular endothelial growth factor levels are lowered in ALS, which can compromise endothelial cell formation and the integrity of the blood–brain barrier. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

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“…Additionally, to improve bioavailability, methods such as nonviral delivery vectors have been used, although they are foreign particles associated with inflammation 18 . A key advantage of EVs is the ability to cross the BBB with less immune response, giving them high therapeutic potential for drug delivery 8 . Specifically, EVs are capable of immunosuppression through the inhibition of natural killer (NK) and CD8 + T cells and enhancement of regulatory T cells 18 .…”

Section: Stem Cells As a Therapeutic For Neurodegenerative Diseasementioning

confidence: 99%

“…EVs derived from hBM‐EPCs have demonstrated promise 8 . In fact, it may be that EVs alone (released by transplanted hBM‐EPCs) play a major role in the aforementioned SOD1 G93A insult amelioration.…”

Section: The Promising Future Of Evs: a Preclinical Literature Reviewmentioning

confidence: 99%

Attenuation of amyotrophic lateral sclerosis via stem cell and extracellular vesicle therapy: An updated review

Lockard,

Gordon,

Schimmel

et al. 2023

Neuroprotection

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Amyotrophic lateral sclerosis (ALS) is a rapidly fatal neurological disease characterized by upper and lower motor neuron degeneration. Though typically idiopathic, familial forms of ALS are commonly composed of a superoxide dismutase 1 (SOD1) mutation. Basic science frequently utilizes SOD1 models in vitro and in vivo to replicate ALS conditions. Therapies are sparse; those that exist in the market extend life minimally, thus driving the demand for research to identify novel therapeutics. Transplantation of stem cells is a promising approach for many diseases and has shown efficacy in SOD1 models and clinical trials. The underlying mechanism for stem cell therapy presents an exciting venue for research investigations. Most notably, the paracrine actions of stem cell‐derived extracellular vesicles (EVs) have been suggested as a potent mitigating factor. This literature review focuses on the most recent preclinical research investigating cell‐free methods for treating ALS. Various avenues are being explored, differing on the EV contents (protein, microRNA, etc.) and on the cell target (astrocyte, endothelial cell, motor neuron‐like cells, etc.), and both molecular and behavioral outcomes are being examined. Unfortunately, EVs may also play a role in propagating ALS pathology. Nonetheless, the overarching goal remains clear: to identify efficient cell‐free techniques to attenuate the deadly consequences of ALS.

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Extracellular vesicle-based therapy for amyotrophic lateral sclerosis

Cited by 13 publications

References 61 publications

Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles

Peripheral extracellular vesicles in neurodegeneration: pathogenic influencers and therapeutic vehicles

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Attenuation of amyotrophic lateral sclerosis via stem cell and extracellular vesicle therapy: An updated review

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