Therapeutic approaches to Celia Encephalopathy (PELD) in murine models “knock in” BSCL2Celia/Celia (Q3148579): Difference between revisions

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(‎Removed claim: summary (P836): Celia encephalopathy is a childhood neurodegenerative disease of infaust prognosis before 9 years due to c.985C>T mutation in the BSCL2/seipin gene. To date, only 7 cases have been reported, of which only one remains alive (8.8 years). Recently, our group has identified a variant of this disorder due to the c.974dup mutation in the same gene in a Spanish girl and an American girl. Previous studies of our group have found, for 5.5 years, that...)
Property / summary
Celia encephalopathy is a childhood neurodegenerative disease of infaust prognosis before 9 years due to c.985C>T mutation in the BSCL2/seipin gene. To date, only 7 cases have been reported, of which only one remains alive (8.8 years). Recently, our group has identified a variant of this disorder due to the c.974dup mutation in the same gene in a Spanish girl and an American girl. Previous studies of our group have found, for 5.5 years, that treatment with human recombinant leptin (LRH) and supplementation with omega-3 fatty acids in the first girl slows neurological involution and improves brain glucose consumption evaluated by PET. On the other hand, our group has found that seipin plays a role in the biogenesis of peroxisomes and in protecting against oxidative stress in the human brain. The objective of this project is to evaluate the treatment with leptin plus omega-3 dietetics associated with drugs that activate peroxisome proliferation (pioglitazone and phenofibrate) in mice “knock in” BSCL2Celia/Celia. Animals and Methods: The neurological phenotypic characterisation of transgenic mice will be performed and treated with leptin, docosahexaenoic acid, pioglitazone, phenofibrate or both prior to the start of the neurological clinic. In the brains of these mice, studies will be conducted using microPET, gene expression studies, protein analysis, confocal and electronic microscopy studies, in vitro electrophysiological studies in neurons of these mice, as well as the study of seipin interaction in neuronal models of Celia encephalopathy generated by CRISPR/Cas9. (English)
 
Property / summary: Celia encephalopathy is a childhood neurodegenerative disease of infaust prognosis before 9 years due to c.985C>T mutation in the BSCL2/seipin gene. To date, only 7 cases have been reported, of which only one remains alive (8.8 years). Recently, our group has identified a variant of this disorder due to the c.974dup mutation in the same gene in a Spanish girl and an American girl. Previous studies of our group have found, for 5.5 years, that treatment with human recombinant leptin (LRH) and supplementation with omega-3 fatty acids in the first girl slows neurological involution and improves brain glucose consumption evaluated by PET. On the other hand, our group has found that seipin plays a role in the biogenesis of peroxisomes and in protecting against oxidative stress in the human brain. The objective of this project is to evaluate the treatment with leptin plus omega-3 dietetics associated with drugs that activate peroxisome proliferation (pioglitazone and phenofibrate) in mice “knock in” BSCL2Celia/Celia. Animals and Methods: The neurological phenotypic characterisation of transgenic mice will be performed and treated with leptin, docosahexaenoic acid, pioglitazone, phenofibrate or both prior to the start of the neurological clinic. In the brains of these mice, studies will be conducted using microPET, gene expression studies, protein analysis, confocal and electronic microscopy studies, in vitro electrophysiological studies in neurons of these mice, as well as the study of seipin interaction in neuronal models of Celia encephalopathy generated by CRISPR/Cas9. (English) / rank
Normal rank
 
Property / summary: Celia encephalopathy is a childhood neurodegenerative disease of infaust prognosis before 9 years due to c.985C>T mutation in the BSCL2/seipin gene. To date, only 7 cases have been reported, of which only one remains alive (8.8 years). Recently, our group has identified a variant of this disorder due to the c.974dup mutation in the same gene in a Spanish girl and an American girl. Previous studies of our group have found, for 5.5 years, that treatment with human recombinant leptin (LRH) and supplementation with omega-3 fatty acids in the first girl slows neurological involution and improves brain glucose consumption evaluated by PET. On the other hand, our group has found that seipin plays a role in the biogenesis of peroxisomes and in protecting against oxidative stress in the human brain. The objective of this project is to evaluate the treatment with leptin plus omega-3 dietetics associated with drugs that activate peroxisome proliferation (pioglitazone and phenofibrate) in mice “knock in” BSCL2Celia/Celia. Animals and Methods: The neurological phenotypic characterisation of transgenic mice will be performed and treated with leptin, docosahexaenoic acid, pioglitazone, phenofibrate or both prior to the start of the neurological clinic. In the brains of these mice, studies will be conducted using microPET, gene expression studies, protein analysis, confocal and electronic microscopy studies, in vitro electrophysiological studies in neurons of these mice, as well as the study of seipin interaction in neuronal models of Celia encephalopathy generated by CRISPR/Cas9. (English) / qualifier
point in time: 12 October 2021
Timestamp+2021-10-12T00:00:00Z
Timezone+00:00
CalendarGregorian
Precision1 day
Before0
After0
 

Revision as of 15:07, 12 October 2021

Project Q3148579 in Spain
Language Label Description Also known as
English
Therapeutic approaches to Celia Encephalopathy (PELD) in murine models “knock in” BSCL2Celia/Celia
Project Q3148579 in Spain

    Statements

    country
    Spain
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    EU contribution
    65,600.0 Euro
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    budget
    82,000.0 Euro
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    co-financing rate
    80.0 percent
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    start time
    1 January 2019
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    end time
    31 March 2022
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    beneficiary name (string)
    FUNDACION INSTITUTO DE INVESTIGACION SANITARIA DE SANTIAGO DE COMPOSTELA
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    beneficiary
    Q3136853
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    coordinate location

    42°52'49.51"N, 8°32'45.10"W
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    postal code
    15078
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    summary
    La encefalopatía de Celia es una enfermedad neurodegenerativa infantil de pronóstico infausto antes de los 9 años debida a la mutación c.985C>T en el gen BSCL2/seipina. A día de hoy sólo se han descrito 7 casos, de los que sólo una permanece con vida (8.8 años). Recientemente, nuestro grupo ha identificado una variante de este trastorno debido a la mutación c.974dup en el mismo gen en una niña española y en una niña norteamericana. Estudios previos de nuestro grupo han comprobado, durante 5.5 años, que el tratamiento con leptina recombinante humana (LRH) y suplementación con ácidos grasos omega-3 en la primera niña enlentece la involución neurológica y mejora el consumo cerebral de glucosa evaluado mediante PET. Por otra parte, nuestro grupo ha encontrado que la seipina juega un papel en la biogénesis de los peroxisomas y en la protección frente al estrés oxidativo en el cerebro humano. El objetivo de este proyecto es evaluar el tratamiento con leptina más omega-3 dietético asociado a fármacos que activen la proliferación de los peroxisomas (pioglitazona y fenofibrato) en ratones “knock in” BSCL2Celia/Celia. Animales y Métodos: Se procederá a la caracterización fenotípica neurológica de los ratones transgénicos y se les tratará, previamente al inicio de la clínica neurológica, con leptina, ácido docosahexaenoico, pioglitazona, fenofibrato o ambos. En los cerebros de estos ratones se realizarán estudios mediante microPET, así como estudios de expresión génica, análisis de proteínas, estudios mediante microscopia confocal y electrónica, y estudios electrofisiológicos in vitro en neuronas de estos ratones, así como el estudio del interactoma de la seipina en modelos neuronales de la encefalopatía de Celia generados mediante CRISPR/Cas9. (Spanish)
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    location (string)
    Santiago de Compostela
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    Identifiers

    Spanish Kohesio ID
    PI18_01890
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