High content analysis in amyotrophic lateral sclerosis

Rinaldi, Federica; Motti, Dario; Ferraiuolo, Laura; Kaspar, Brian K.

doi:10.1016/j.mcn.2016.12.001

Cited by 13 publications

(7 citation statements)

References 160 publications

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“…Regarding causes of death, no repeated respiratory problems (pneumonia) were detected, as in other studies on rare genetic diseases [16, 17]. Therefore, Spoan syndrome is different from conditions such as Duchenne muscular dystrophy, in which the life expectancy is limited to two or three decades as a function of cardiac and respiratory involvement [18], and amyotrophic lateral sclerosis, with a life expectancy of 2 to 5 years after diagnosis [19, 20]. Some patients exhibited dysphagia, none required a feeding tube.…”

Section: Discussionmentioning

confidence: 86%

Motor impairment in a rare form of spastic paraplegia (Spoan syndrome): a 10-year follow-up

et al. 2019

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BackgroundSpastic paraplegia, optic atrophy and neuropathy (Spoan syndrome) is an autosomal recessive disease with approximately 70 cases recorded in Brazil and Egypt.MethodsThis is a prospective longitudinal study performed with 47 patients affected with Spoan syndrome of seven communities of Rio Grande do Norte (Brazil) to investigate changes in motor function based on comparative data obtained from a 10-year follow-up.ResultsThe mean age of the participants was 47.21 ± 12.42 years old, and the mean age at loss of ambulation and hand function were 10.78 ± 5.55 and 33.58 ± 17.47 years old, respectively. Spearman’s correlation analysis between the score on the Modified Barthel Index and the investigated variables evidenced statistical significance for age (p < 0.001) and right- and left-hand grip strength (p = 0.042 and p = 0.021, respectively). Statistical significance was not evidenced for the remainder of the variables, including age at onset of symptoms (p = 0.634), age at loss of ambulation (p = 0.664) and age at loss of hand function (p = 0.118).ConclusionsOur analysis allows asserting that the participants exhibited slight dependence until age 35. The greatest losses occurred from ages 35 to 41, and starting at 50, practically all patients become completely dependent. These findings are relevant for determining the prognosis as well as suitable treatment, rehabilitation and assistive technology for these individuals.

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Section: Discussionmentioning

confidence: 86%

Motor impairment in a rare form of spastic paraplegia (Spoan syndrome): a 10-year follow-up

et al. 2019

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“…The astrocytes can be used for mechanistic studies, metabolic studies or drug testing assays and are usually grown as monolayers. Moreover, astrocytes can be combined in co-culture systems with mouse or human neurons to assess the impact of astrocytes on neuronal survival and morphology, both of which are good readouts for drug testing 34 .…”

Section: Discussionmentioning

confidence: 99%

In vitro Modeling for Neurological Diseases using Direct Conversion from Fibroblasts to Neuronal Progenitor Cells and Differentiation into Astrocytes

Dennys

Sierra-Delgado

Ray

et al. 2021

JoVE

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Research on neurological disorders focuses primarily on the impact of neurons on disease mechanisms. Limited availability of animal models severely impacts the study of cell type specific contributions to disease. Moreover, animal models usually do not reflect variability in mutations and disease courses seen in human patients. Reprogramming methods for generation of induced pluripotent stem cells (iPSCs) have revolutionized patient specific research and created valuable tools for studying disease mechanisms. However, iPSC technology has disadvantages such as time, labor commitment, clonal selectivity and loss of epigenetic markers.Recent modifications of these methods allow more direct generation of cell lineages or specific cell types, bypassing clonal isolation or a pluripotent stem cell state. We have developed a rapid direct conversion method to generate induced Neuronal Progenitor Cells (iNPCs) from skin fibroblasts utilizing retroviral vectors in combination with neuralizing media. The iNPCs can be differentiated into neurons (iNs) oligodendrocytes (iOs) and astrocytes (iAs). iAs production facilitates rapid drug and disease mechanism testing as differentiation from iNPCs only takes 5 days.Moreover, iAs are easy to work with and are generated in pure populations at large numbers. We developed a highly reproducible co-culture assay using mouse GFP + neurons and patient derived iAs to evaluate potential therapeutic strategies for numerous neurological and neurodegenerative disorders. Importantly, the iA assays are scalable to 384-well format facilitating the evaluation of multiple small molecules in one plate. This approach allows simultaneous therapeutic evaluation of multiple patient cell lines with diverse genetic background. Easy production and storage of iAs and capacity to screen multiple compounds in one assay renders this methodology adaptable for personalized medicine.

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“…Regarding causes of death, no repeated respiratory problems (pneumonia) were detected, as in other studies on rare genetic diseases [16], [17]. Therefore, Spoan syndrome is different from conditions such as Duchenne muscular dystrophy, in which the life expectancy is limited to two or three decades as a function of cardiac and respiratory involvement [18], and amyotrophic lateral sclerosis, with a life expectancy of two to five years after diagnosis [19], [20]. Some patients exhibited dysphagia, none required a feeding tube.…”

Section: Discussionmentioning

confidence: 68%

Motor impairment in a rare form of spastic paraplegia (Spoan syndrome): a 10-year follow-up

Galvão

Cavalcante

Olinda

et al. 2019

Preprint

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Background: Spastic paraplegia, optic atrophy and neuropathy (Spoan syndrome) is an autosomal recessive disease with approximately 70 cases recorded in Brazil and Egypt. Methods: This is a prospective longitudinal study performed with 47 patients affected with Spoan syndrome of seven communities of Rio Grande do Norte (Brazil) to investigate changes in motor function based on comparative data obtained from a 10-year follow-up. Results: The mean age of the participants was 47.21±12.42 years old, and the mean age at loss of ambulation and hand function were 10.78±5.55 and 33.58±17.47 years old, respectively. Spearman’s correlation analysis between the score on the Modified Barthel Index and the investigated variables evidenced statistical significance for age (p<0.001) and right- and left-hand grip strength (p=0.042 and p=0.021, respectively). Statistical significance was not evidenced for the remainder of the variables, including age at onset of symptoms (p=0.634), age at loss of ambulation (p=0.664) and age at loss of hand function (p=0.118). Conclusions: Our analysis allows asserting that the participants exhibited slight dependence until age 35. The greatest losses occurred from ages 35 to 41, and starting at 50, practically all patients become completely dependent. These findings are relevant for determining the prognosis as well as suitable treatment, rehabilitation and assistive technology for these individuals.

show abstract

High content analysis in amyotrophic lateral sclerosis

Cited by 13 publications

References 160 publications

Motor impairment in a rare form of spastic paraplegia (Spoan syndrome): a 10-year follow-up

Motor impairment in a rare form of spastic paraplegia (Spoan syndrome): a 10-year follow-up

In vitro Modeling for Neurological Diseases using Direct Conversion from Fibroblasts to Neuronal Progenitor Cells and Differentiation into Astrocytes

Motor impairment in a rare form of spastic paraplegia (Spoan syndrome): a 10-year follow-up

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