Spinal muscular atrophy

Lunn, Mitchell R.; Wang, Ching H.

doi:10.1016/s0140-6736(08)60921-6

Cited by 748 publications

(694 citation statements)

References 151 publications

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“…Spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders and the most common genetic cause of infant mortality [1][2][3]. SMA is caused by loss of the survival of motoneuron (SMN) protein, resulting in the degeneration of alpha motoneurons in spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Brief Report: Phenotypic Rescue of Induced Pluripotent Stem Cell-Derived Motoneurons of a Spinal Muscular Atrophy Patient

et al. 2011

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Spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders in humans and is a common genetic cause of infant mortality. The disease is caused by loss of the survival of motoneuron (SMN) protein, resulting in the degeneration of alpha motoneurons in spinal cord and muscular atrophy in the limbs and trunk. One function of SMN involves RNA splicing. It is unclear why a deficiency in a housekeeping function such as RNA splicing causes profound effects only on motoneurons but not on other cell types. One difficulty in studying SMA is the scarcity of patient's samples. The discovery that somatic cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) raises the intriguing possibility of modeling human diseases in vitro. We reported the establishment of five iPSC lines from the fibroblasts of a type 1 SMA patient. Neuronal cultures derived from these SMA iPSC lines exhibited a reduced capacity to form motoneurons and an abnormality in neurite outgrowth. Ectopic SMN expression in these iPSC lines restored normal motoneuron differentiation and rescued the phenotype of delayed neurite outgrowth. These results suggest that the observed abnormalities are indeed caused by SMN deficiency and not by iPSC clonal variability. Further characterization of the cellular and functional deficits in motoneurons derived from these iPSCs may accelerate the exploration of the underlying mechanisms of SMA pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Brief Report: Phenotypic Rescue of Induced Pluripotent Stem Cell-Derived Motoneurons of a Spinal Muscular Atrophy Patient

et al. 2011

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“…The disease is caused by deletions of the SMN1 gene, resulting in a decreased level of survival of motor neuron (SMN) protein, which eventually leads to the loss of motor neurons and the consequent denervation of the axial and limb muscles. This loss manifests clinically as muscle atrophy and weakness, dysphagia and respiratory failure in severe cases [24] . Researchers have screened for compounds that elevate SMN levels in various engineered cell lines and patient fibroblasts, [25] and demonstrated that SMA motor neurons derived from iPSCs developed normally but were more susceptible to degeneration accompanied by a reduction in SMN aggregates.…”

Section: Neurological Diseasesmentioning

confidence: 99%

iPSCs and small molecules: a reciprocal effort towards better approaches for drug discovery

Zhang

Xie

2013

Acta Pharmacol Sin

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The revolutionary induced pluripotent stem cell (iPSC) technology provides a new path for cell replacement therapies and drug screening. Patient-specific iPSCs and subsequent differentiated cells manifesting disease phenotypes will finally position human disease pathology at the core of drug discovery. Cells used to test the toxic effects of drugs can also be generated from normal iPSCs and provide a much more accurate and cost-effective system than many animal models. Here, we highlight the recent progress in iPSC-based cell therapy, disease modeling and drug evaluations. In addition, we discuss the use of small molecule drugs to improve the generation of iPSCs and understand the reprogramming mechanism. It is foreseeable that the interplay between iPSC technology and small molecule compounds will push forward the applications of iPSC-based therapy and screening systems in the real world and eventually revolutionize the methods used to treat diseases.

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“…4 Unidad de Neurología Fax: 56-2-6108413 E-mail: ccastiglioni@clc.c L a atrofi a muscular espinal (AME) es una enfermedad neurodegenerativa que afecta las neuronas motoras del asta anterior de la médula espinal y constituye la segunda causa de enfermedad autosómica recesiva después de la fi brosis quística 1 . Es la causa genética más frecuente de mortalidad en lactantes 1,2 , con una incidencia mundial descrita entre 1/6.000 y 1/10.000 nacimientos y una tasa de portadores entre 1/35 y 1/50 [1][2][3] . En nuestro país no existen datos de su prevalencia.…”

Section: Instituto Nacional Deunclassified

“…Clínicamente se caracteriza por una debilidad y atrofi a muscular generalizada de predominio proximal, que comienza en extremidades inferiores, extendiéndose a tronco y extremidades superiores en grado variable según el tipo clínico 2,3 . La capacidad cognitiva de estos pacientes está siempre preservada 4 .…”

Section: Instituto Nacional Deunclassified

Atrofia muscular espinal: Caracterización clínica, electrofisiológica y molecular de 26 pacientes

et al. 2011

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Spinal muscular atrophy

Cited by 748 publications

References 151 publications

Brief Report: Phenotypic Rescue of Induced Pluripotent Stem Cell-Derived Motoneurons of a Spinal Muscular Atrophy Patient

Brief Report: Phenotypic Rescue of Induced Pluripotent Stem Cell-Derived Motoneurons of a Spinal Muscular Atrophy Patient

iPSCs and small molecules: a reciprocal effort towards better approaches for drug discovery

Atrofia muscular espinal: Caracterización clínica, electrofisiológica y molecular de 26 pacientes

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