Very severe spinal muscular atrophy (Type 0)

Dakhoul, Suleiman Al

doi:10.4103/2231-0770.197512

Cited by 11 publications

(9 citation statements)

References 9 publications

(14 reference statements)

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“…Symptoms of the most severe forms of SMA (types 0 and I) appear from the late prenatal period to the early postnatal period. [4][5][6] Martínez-Hernández et al 22 reported a prenatal delay of muscle maturation in SMA that emphasizes the importance of initiating treatment as early as possible. Therefore, we investigated the applicability of fetal gene therapy for the prevention of SMA symptoms using a mouse model.…”

Section: Discussionmentioning

confidence: 99%

“…Symptoms of the most severe forms of SMA (types 0 and I) appear from the late prenatal to the early postnatal period and include: decreased movement at prenatal stage, fetal akinesia sequence, congenital contractures, and postnatal respiratory insufficiency. [4][5][6] Fetal gene therapy presents as a promising approach to prevent irreversible tissue damage caused by early onset genetic disorders that require early childhood treatments, such as SMA, Duchenne muscular dystrophy (DMD), CF, and lysosomal storage diseases. Restoring the defective gene function at an older age is only capable of halting progression of the disease but is not generally able to reverse the pathological alterations and, therefore, cannot provide complete cures for these diseases.…”

Section: Introductionmentioning

confidence: 99%

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Fetal Gene Therapy Using a Single Injection of Recombinant AAV9 Rescued SMA Phenotype in Mice

et al. 2019

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Symptoms of spinal muscular atrophy (SMA) disease typically begin in the late prenatal or the early postnatal period of life. The intrauterine (IU) correction of gene expression, fetal gene therapy, could offer effective gene therapy approach for early onset diseases. Hence, the overall goal of this study was to investigate the efficacy of human survival motor neuron (hSMN) gene expression after IU delivery in SMA mouse embryos. First, we found that IU-intracerebroventricular (i.c.v.) injection of adeno-associated virus serotype-9 (AAV9)-EGFP led to extensive expression of EGFP protein in different parts of the CNS with a great number of transduced neural stem cells. Then, to implement the fetal gene therapy, mouse fetuses received a single i.c.v. injection of a single-stranded (ss) or self-complementary (sc) AAV9-SMN vector that led to a lifespan of 93 (median of 63) or 171 (median 105) days for SMA mice. The muscle pathology and number of the motor neurons also improved in both study groups, with slightly better results coming from scAAV treatment. Consequently, fetal gene therapy may provide an alternative therapeutic approach for treating inherited diseases such as SMA that lead to prenatal death or lifelong irreversible damage.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fetal Gene Therapy Using a Single Injection of Recombinant AAV9 Rescued SMA Phenotype in Mice

et al. 2019

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“…The copy number of SMN2 gene modifies the severity of the disease phenotype as a high number of SMN2 copies is related to milder phenotypes [40,42]. For instance, SMA type I patients generally have one or two SMN2 copies, while SMA type III/IV patients have more than four copies [43,44]. Nevertheless, this inverse relationship is not always true, as a few patients with two SMN2 copies showed milder SMA phenotypes, while there have also been patients with three SMN2 copies that have been defined as type I [21,[45][46][47].…”

Section: Disease Etiologymentioning

confidence: 99%

Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review

Gandhi

Lee

et al. 2021

IJMS

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Spinal muscular atrophy (SMA), one of the leading inherited causes of child mortality, is a rare neuromuscular disease arising from loss-of-function mutations of the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein. When lacking the SMN protein in neurons, patients suffer from muscle weakness and atrophy, and in the severe cases, respiratory failure and death. Several therapeutic approaches show promise with human testing and three medications have been approved by the U.S. Food and Drug Administration (FDA) to date. Despite the shown promise of these approved therapies, there are some crucial limitations, one of the most important being the cost. The FDA-approved drugs are high-priced and are shortlisted among the most expensive treatments in the world. The price is still far beyond affordable and may serve as a burden for patients. The blooming of the biomedical data and advancement of computational approaches have opened new possibilities for SMA therapeutic development. This article highlights the present status of computationally aided approaches, including in silico drug repurposing, network driven drug discovery as well as artificial intelligence (AI)-assisted drug discovery, and discusses the future prospects.

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“…SMA is divided to 4 types based on the age of onset and maximum motor function achieved. SMA type 1 includes very weak infants with reduced fetal movements in utero, inability to sit independently and short survival time (102,104). Type 2 of SMA includes non-ambulant patients able to sit but unable to walk independently, while SMA type 3 refers to ambulant patients with childhood onset of disease (102).…”

Section: Spinal Muscular Atrophymentioning

confidence: 99%

Rare Neurological Diseases: an Overreview of Pathophysiology, Epidemiology, Clinical Features and Pharmacoeconomic Considerations in the Treating

Gutić

Milidrag

Cikotic³

et al. 2021

Serbian Journal of Experimental and Clinical Research

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Rare diseases (RD) are serious chronic diseases affecting small number of people compared to the general population. There are between 6000 and 8000 RDs, which affect about 400 million people worldwide. Drugs used for causal treatment of RDs are called orphan drugs. RDs bear great clinical and economic burden for patients, their families, healthcare systems and society overall. There are at least two reasons for the high cost of treatment of RDs. First, there is no causal therapy for majority of RDs, so exacerbations, complications, and hospitalizations in those patients are common. The second reason is high price of available orphan drugs, which are not cost-effective when traditional pharmacoeconomic evaluation is employed. The pharmacoeconomic aspect of the treatment of RDs is especially important in the field of neurology, since at least one fifth of all RDs is composed of neurological conditions. The aim of this paper was to provide a concise overview of the pathophysiological, epidemiological and clinical characteristics of some of the most important and common rare neurological diseases, with special reference to their impact on society and economy.

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Very severe spinal muscular atrophy (Type 0)

Cited by 11 publications

References 9 publications

Fetal Gene Therapy Using a Single Injection of Recombinant AAV9 Rescued SMA Phenotype in Mice

Fetal Gene Therapy Using a Single Injection of Recombinant AAV9 Rescued SMA Phenotype in Mice

Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review

Rare Neurological Diseases: an Overreview of Pathophysiology, Epidemiology, Clinical Features and Pharmacoeconomic Considerations in the Treating

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