RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis

Mathis, Stéphane; Masson, Gwendal Le

doi:10.3390/biomedicines6010009

Cited by 21 publications

(16 citation statements)

References 78 publications

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“…Nevertheless, emerging strategies for molecules design and modification, types of administration and delivery to the CNS have been described and actively used in vivo . Antisense oligonucleotides (ASOs) have been administrated to the CNS via intracerebroventricular or intrathecal infusion of CSF into rodent and non-human primate animal models for tauopathy, HD, ALS and spinal muscular atrophy (SMA) [92,93,94,95,96]. More importantly, clinical trials in patients with ALS or SMA that involve intrathecal delivery of ASOs against protein-coding transcripts have demonstrated the promise of therapeutically targeting RNAs [97,98,99].…”

Section: Circular Rnas As Neurological Disease Biomarkers and Thermentioning

confidence: 99%

Exploring the Regulatory Role of Circular RNAs in Neurodegenerative Disorders

D’Ambra

Capauto

Morlando

2019

IJMS

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Circular RNAs (circRNAs) are a distinctive class of regulatory non-coding RNAs characterised by the presence of covalently closed ends. They are evolutionary conserved molecules, and although detected in different tissues, circRNAs resulted specifically enriched in the nervous system. Recent studies have shown that circRNAs are dynamically modulated during neuronal development and aging, that circRNAs are enriched at synaptic levels and resulted modulated after synaptic plasticity induction. This has suggested that circRNAs might play an important role in neuronal specification and activity. Despite the exact function of circRNAs is still poorly understood, emerging evidence indicates that circRNAs have important regulatory functions that might extensively contribute to the dynamic modulation of gene expression that supports neuronal pathways. More interestingly, deregulation of circRNAs expression has been linked with various pathological conditions. In this review, we describe current advances in the field of circRNA biogenesis and function in the nervous system both in physiological and in pathological conditions, and we specifically lay out their association with neurodegenerative diseases. Furthermore, we discuss the opportunity to exploit circRNAs for innovative therapeutic approaches and, due to their high stability, to use circRNAs as suitable biomarkers for diagnosis and disease progression.

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Section: Circular Rnas As Neurological Disease Biomarkers and Thermentioning

confidence: 99%

Exploring the Regulatory Role of Circular RNAs in Neurodegenerative Disorders

D’Ambra

Capauto

Morlando

2019

IJMS

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“…However, in the past couple years, there has been a real encouragement in witnessing potentially efficacious treatments, such as Masitinib and Pimozide (Trias et al, 2016; Patten et al, 2017; Petrov et al, 2017) claiming to demonstrate clinical benefit. Furthermore, RNA-targeted therapies are currently intensively being evaluated as potential strategies for treating this ALS (Schoch and Miller, 2017; Mathis and Le Masson, 2018). There is indeed hope to have new and potentially more effective treatment options available for ALS in the near future.…”

Section: Introductionmentioning

confidence: 99%

RNA Dysregulation in Amyotrophic Lateral Sclerosis

2019

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Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease and is characterized by the degeneration of upper and lower motor neurons. It has become increasingly clear that RNA dysregulation is a key contributor to ALS pathogenesis. The major ALS genes SOD1, TARDBP, FUS, and C9orf72 are involved in aspects of RNA metabolism processes such as mRNA transcription, alternative splicing, RNA transport, mRNA stabilization, and miRNA biogenesis. In this review, we highlight the current understanding of RNA dysregulation in ALS pathogenesis involving these major ALS genes and discuss the potential of therapeutic strategies targeting disease RNAs for treating ALS.

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“…), providing hope of a "polytherapy" approach with the hope to slow the evolution down and prolongs survival [4,7]. e recent progress in gene therapy also highlight promising future antisense oligonucleotide and viral therapeutic strategies for treating ALS (particularly familial ALS) [8]. ese new therapies will likely to be more effective if started in the earlier phase of the disease, which should then be diagnosed quickly.…”

Section: Introductionmentioning

confidence: 99%

Minimizing the Diagnostic Delay in Amyotrophic Lateral Sclerosis: The Role of Nonneurologist Practitioners

Matharan

Mathis

Bonabaud

et al. 2020

Neurology Research International

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Introduction. Amyotrophic lateral sclerosis (ALS), usually fatal in a few years, is a neurodegenerative disorder where the diagnostic delay, although variable according to the studies, remains too long. The main objective of this study was to determine the average time to diagnose ALS and the role of each physician, general practitioner (GP), or specialist (neurologist or not) involved in the management of these patients. The secondary objective was to propose some simple schemes to quickly identify an ALS suspicion with the aim to reduce this delay. Patients and Methods. This retrospective study evaluated the diagnostic delay (and other intermediate delays) of 90 ALS patients registered in the ALS Center of Bordeaux (France) in 2013. The main clinical signs encountered (and their order of appearance) were studied. Results. The average diagnostic delay was 17 months, with a median diagnostic delay of 12 months. The average diagnostic delay was 2.7 months between the first symptoms and the first complaint to GP, followed by an additional 6.5 month delay before the patient’s first visit to a neurologist. This period could be shortened, especially if GP performed additional tests quickly (p=0.01), as the time spent consulting various specialists often extends this crucial step. Overall, diagnostic delay accounted for 40% of the total duration of the disease progression. Conclusion. In relation to total survival time, the diagnostic delay of ALS appears to be proportionately very long, sometimes longer than that observed in previous studies (because it also included the total delay to diagnostic or treatment initiation). The rapid execution of useful additional tests by the first medical doctor, often GP (with the help of a neurologist), considerably reduces the diagnostic delay. The central role of GP seems to be crucial in the management of patients with ALS. The main objective is, of course, to initiate appropriate treatment and care as soon as possible. Finally, based on our results, we also provide a short practical diagram to help nonneurologist practitioners to quickly discuss the diagnosis of ALS in case of some specific symptoms (“red flags”).

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RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis

Cited by 21 publications

References 78 publications

Exploring the Regulatory Role of Circular RNAs in Neurodegenerative Disorders

Exploring the Regulatory Role of Circular RNAs in Neurodegenerative Disorders

RNA Dysregulation in Amyotrophic Lateral Sclerosis

Minimizing the Diagnostic Delay in Amyotrophic Lateral Sclerosis: The Role of Nonneurologist Practitioners

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