Non-Viral Vector-Mediated Gene Therapy for ALS: Challenges and Future Perspectives

Ediriweera, Gayathri R.; Chen, Liyu; Yerbury, Justin J.; Thurecht, Kristofer J.; Vine, Kara L.

doi:10.1021/acs.molpharmaceut.1c00297

Cited by 38 publications

(23 citation statements)

References 143 publications

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“…The effects observed in mice, such as preventing weight loss and impaired neuromuscular function, as well as increased survival, support the effectiveness of this technology [ 101 ]. The therapeutic approach using RNAi has the potential to be another form of gene therapy for ALS but still needs to overcome such difficulties as in vivo instability, lack of siRNA specificity and potential toxicity of RNAi-based technologies [ 102 ].…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Gene Therapy in ALS and SMA: Advances, Challenges and Perspectives

Lejman

Panuciak

Nowicka

et al. 2023

IJMS

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Gene therapy is defined as the administration of genetic material to modify, manipulate gene expression or alter the properties of living cells for therapeutic purposes. Recent advances and improvements in this field have led to many breakthroughs in the treatment of various diseases. As a result, there has been an increasing interest in the use of these therapies to treat motor neuron diseases (MNDs), for which many potential molecular targets have been discovered. MNDs are neurodegenerative disorders that, in their most severe forms, can lead to respiratory failure and death, for instance, spinal muscular atrophy (SMA) or amyotrophic lateral sclerosis (ALS). Despite the fact that SMA has been known for many years, it is still one of the most common genetic diseases causing infant mortality. The introduction of drugs based on ASOs—nusinersen; small molecules—risdiplam; and replacement therapy (GRT)—Zolgensma has shown a significant improvement in both event-free survival and the quality of life of patients after using these therapies in the available trial results. Although there is still no drug that would effectively alleviate the course of the disease in ALS, the experience gained from SMA gene therapy gives hope for a positive outcome of the efforts to produce an effective and safe drug. The aim of this review is to present current progress and prospects for the use of gene therapy in the treatment of both SMA and ALS.

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Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Gene Therapy in ALS and SMA: Advances, Challenges and Perspectives

Lejman

Panuciak

Nowicka

et al. 2023

IJMS

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“…In this research, the brain region targeted for BBB opening was the eloquent primary motor cortex, and the process was found to be safe, feasible, and reversible. For patients with ALS, BBB opening is used to introduce agents such as nonviral vectors that transport therapeutic genetic elements into neurons; it is therefore essential that these agents are not damaged as they travel through the BBB ( 104 ).…”

Section: Fus-mediated Bbb Openingmentioning

confidence: 99%

Clinical Intervention Using Focused Ultrasound (FUS) Stimulation of the Brain in Diverse Neurological Disorders

et al. 2022

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Various surgical techniques and pharmaceutical treatments have been developed to improve the current technologies of treating brain diseases. Focused ultrasound (FUS) is a new brain stimulation modality that can exert a therapeutic effect on diseased brain cells, with this effect ranging from permanent ablation of the pathological neural circuit to transient excitatory/inhibitory modulation of the neural activity depending on the acoustic energy of choice. With the development of intraoperative imaging technology, FUS has become a clinically available noninvasive neurosurgical option with visual feedback. Over the past 10 years, FUS has shown enormous potential. It can deliver acoustic energy through the physical barrier of the brain and eliminate abnormal brain cells to treat patients with Parkinson's disease and essential tremor. In addition, FUS can help introduce potentially beneficial therapeutics at the exact brain region where they need to be, bypassing the brain's function barrier, which can be applied for a wide range of central nervous system disorders. In this review, we introduce the current FDA-approved clinical applications of FUS, ranging from thermal ablation to blood barrier opening, as well as the emerging applications of FUS in the context of pain control, epilepsy, and neuromodulation. We also discuss the expansion of future applications and challenges. Broadening FUS technologies requires a deep understanding of the effect of ultrasound when targeting various brain structures in diverse disease conditions in the context of skull interface, anatomical structure inside the brain, and pathology.

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“…Some scholars suggested that EVs can act as a non-viral vector for the delivery of genetic material to treat ALS due to their ability to transport various cellular entities across the BBB. Surprisingly, the research on using EVs for gene delivery in the treatment of ALS is very few ( Ediriweera et al, 2021 ). Nevertheless, this aspect of research work has become an interesting subject with the thriving advances in nanotechnology.…”

Section: Extracellular Vesicles As Drug Delivery Vehicle For Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Extracellular Vesicles as Innovative Treatment Strategy for Amyotrophic Lateral Sclerosis

Wang

Ren

et al. 2021

Front. Cell Dev. Biol.

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Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron degenerative disease, and it is hard to diagnose in the early stage, and treatment means are limited, and the treatment effect is unsatisfactory. Therefore, exploring a new effective treatment strategy is urgently needed for ALS patients. Extracellular vesicles (EVs) are a heterogeneous group of natural membrane vesicles containing many bioactive substances, and they play important roles in the paracrine pathway and exhibit neuroprotection effects. A growing body of evidence shows that EVs have great application potential in diagnosis, treatment, and drug delivery in ALS, and they represent an innovative treatment strategy for ALS. In this review, we will briefly introduce the biogenesis of EVs and focus on discussing the role of EVs in ALS treatment to further enrich and boost the development of EVs as an innovative treatment strategy for ALS.

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Non-Viral Vector-Mediated Gene Therapy for ALS: Challenges and Future Perspectives

Cited by 38 publications

References 143 publications

Gene Therapy in ALS and SMA: Advances, Challenges and Perspectives

Gene Therapy in ALS and SMA: Advances, Challenges and Perspectives

Clinical Intervention Using Focused Ultrasound (FUS) Stimulation of the Brain in Diverse Neurological Disorders

Extracellular Vesicles as Innovative Treatment Strategy for Amyotrophic Lateral Sclerosis

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