Q3144292 (Q3144292): Difference between revisions
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(Created claim: summary (P836): Little is known about the molecular mechanisms involved in early neurodegeneration in the Mucopolysaccharidosis (MPS). On the other hand, long-term studies in MPS VII models suggest that bone pathology in the spine may be difficult to correct, even with elevated serum enzyme levels. The main objective of this project is on the one hand to understand how the accumulation of glycosaminoglycans in lysosomes leads to neurodegeneration and on the oth...) |
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Little is known about the molecular mechanisms involved in early neurodegeneration in the Mucopolysaccharidosis (MPS). On the other hand, long-term studies in MPS VII models suggest that bone pathology in the spine may be difficult to correct, even with elevated serum enzyme levels. The main objective of this project is on the one hand to understand how the accumulation of glycosaminoglycans in lysosomes leads to neurodegeneration and on the other to check whether new gene therapy strategies can restore neuronal function and prevent the progression of bone pathology in a mouse model MPS VII. To do this we will use adeno-associated vectors to transfer the therapeutic gene to the cerebrospinal fluid (CSF) of mice MPS VII using a non-invasive method such as intrathecal administration and correlate the levels of recombinant enzyme in tissues, CSF and blood with the recovery of neuronal function and progression of bone deformation. In primary brain neuron cultures we will study the homeostasis of these neurons using markers of autophagia and the content and synaptic function to identify which pathways are affected and find new therapeutic targets. The preclinical data we will obtain will allow us to advance the proposal of a gene therapy clinical trial for MPS VII. (English) | |||||||||||||||
| Property / summary: Little is known about the molecular mechanisms involved in early neurodegeneration in the Mucopolysaccharidosis (MPS). On the other hand, long-term studies in MPS VII models suggest that bone pathology in the spine may be difficult to correct, even with elevated serum enzyme levels. The main objective of this project is on the one hand to understand how the accumulation of glycosaminoglycans in lysosomes leads to neurodegeneration and on the other to check whether new gene therapy strategies can restore neuronal function and prevent the progression of bone pathology in a mouse model MPS VII. To do this we will use adeno-associated vectors to transfer the therapeutic gene to the cerebrospinal fluid (CSF) of mice MPS VII using a non-invasive method such as intrathecal administration and correlate the levels of recombinant enzyme in tissues, CSF and blood with the recovery of neuronal function and progression of bone deformation. In primary brain neuron cultures we will study the homeostasis of these neurons using markers of autophagia and the content and synaptic function to identify which pathways are affected and find new therapeutic targets. The preclinical data we will obtain will allow us to advance the proposal of a gene therapy clinical trial for MPS VII. (English) / rank | |||||||||||||||
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| Property / summary: Little is known about the molecular mechanisms involved in early neurodegeneration in the Mucopolysaccharidosis (MPS). On the other hand, long-term studies in MPS VII models suggest that bone pathology in the spine may be difficult to correct, even with elevated serum enzyme levels. The main objective of this project is on the one hand to understand how the accumulation of glycosaminoglycans in lysosomes leads to neurodegeneration and on the other to check whether new gene therapy strategies can restore neuronal function and prevent the progression of bone pathology in a mouse model MPS VII. To do this we will use adeno-associated vectors to transfer the therapeutic gene to the cerebrospinal fluid (CSF) of mice MPS VII using a non-invasive method such as intrathecal administration and correlate the levels of recombinant enzyme in tissues, CSF and blood with the recovery of neuronal function and progression of bone deformation. In primary brain neuron cultures we will study the homeostasis of these neurons using markers of autophagia and the content and synaptic function to identify which pathways are affected and find new therapeutic targets. The preclinical data we will obtain will allow us to advance the proposal of a gene therapy clinical trial for MPS VII. (English) / qualifier | |||||||||||||||
point in time: 12 October 2021
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Revision as of 14:01, 12 October 2021
Project Q3144292 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | No label defined |
Project Q3144292 in Spain |
Statements
60,750.0 Euro
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121,500.0 Euro
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50.0 percent
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1 January 2016
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31 March 2020
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UNIVERSIDAD AUTONOMA DE BARCELONA
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41°29'27.71"N, 2°8'15.00"E
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08266
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Poco se sabe acerca de los mecanismos moleculares implicados en la temprana neurodegeneración en las Mucopolisacharidosis (MPS). Por otra parte, estudios a largo plazo en modelos de MPS VII sugieren que la patología ósea en la columna vertebral puede ser difícil de corregir, incluso con niveles séricos elevados del enzima. El objetivo principal de este proyecto es por una parte entender cómo la acumulación de los glicosaminoglicanos en los lisosomas conduce a la neurodegeneración y por otra comprobar si nuevas estrategias de terapia génica pueden restaurar la función neuronal y evitar la progresión de la patología ósea en un modelo de ratón MPS VII. Para ello utilizaremos vectores adeno-asociados para transferir el gen terapéutico al líquido cefalorraquídeo (LCR) de ratones MPS VII mediante un método poco invasivo como es la administración intratecal y correlacionaremos los niveles de enzima recombinante en tejidos, LCR y sangre con la recuperación de la función neuronal y la progresión de la deformación ósea. En cultivos primarios de neuronas del cerebro estudiaremos la homeostasis de estas neuronas mediante marcadores de autofagia y del contenido y función sináptica para identificar qué vías están afectadas y encontrar nuevas dianas terapéuticas. Los datos preclínicos que obtendremos nos permitirán avanzar en la propuesta de un ensayo clínico de terapia génica para MPS VII. (Spanish)
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Little is known about the molecular mechanisms involved in early neurodegeneration in the Mucopolysaccharidosis (MPS). On the other hand, long-term studies in MPS VII models suggest that bone pathology in the spine may be difficult to correct, even with elevated serum enzyme levels. The main objective of this project is on the one hand to understand how the accumulation of glycosaminoglycans in lysosomes leads to neurodegeneration and on the other to check whether new gene therapy strategies can restore neuronal function and prevent the progression of bone pathology in a mouse model MPS VII. To do this we will use adeno-associated vectors to transfer the therapeutic gene to the cerebrospinal fluid (CSF) of mice MPS VII using a non-invasive method such as intrathecal administration and correlate the levels of recombinant enzyme in tissues, CSF and blood with the recovery of neuronal function and progression of bone deformation. In primary brain neuron cultures we will study the homeostasis of these neurons using markers of autophagia and the content and synaptic function to identify which pathways are affected and find new therapeutic targets. The preclinical data we will obtain will allow us to advance the proposal of a gene therapy clinical trial for MPS VII. (English)
12 October 2021
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Cerdanyola del Vallès
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Identifiers
PI15_01271
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