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Fetal gene therapy ...
Fetal gene therapy for neurodegenerative disease of infants
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- Massaro, Giulia (författare)
- University College London
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- Mattar, Citra N.Z. (författare)
- National University of Singapore
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- Wong, Andrew M.S. (författare)
- King's College London
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- Sirka, Ernestas (författare)
- University College London
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- Buckley, Suzanne M.K. (författare)
- University College London
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- Herbert, Bronwen R. (författare)
- Imperial College London
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- Karlsson, Stefan (författare)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Perocheau, Dany P. (författare)
- University College London
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- Burke, Derek (författare)
- University College London
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- Heales, Simon (författare)
- University College London
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- Richard-Londt, Angela (författare)
- University College London
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- Brandner, Sebastian (författare)
- University College London
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- Huebecker, Mylene (författare)
- University of Oxford
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- Priestman, David A. (författare)
- University of Oxford
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- Platt, Frances M. (författare)
- University of Oxford
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- Mills, Kevin (författare)
- University College London
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- Biswas, Arijit (författare)
- National University of Singapore
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- Cooper, Jonathan D. (författare)
- Jonsson Comprehensive Cancer Center,Washington University in St. Louis,King's College London
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- Chan, Jerry K.Y. (författare)
- Duke–NUS Medical School,National University of Singapore
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- Cheng, Seng H. (författare)
- Sanofi-Synthelabo, Inc.
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- Waddington, Simon N. (författare)
- University of the Witwatersrand
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- Rahim, Ahad A. (författare)
- University College London
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(creator_code:org_t)
- 2018-07-16
- 2018
- Engelska.
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 24:9, s. 1317-1323
- Relaterad länk:
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http://dx.doi.org/10...
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https://europepmc.or...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- For inherited genetic diseases, fetal gene therapy offers the potential of prophylaxis against early, irreversible and lethal pathological change. To explore this, we studied neuronopathic Gaucher disease (nGD), caused by mutations in GBA. In adult patients, the milder form presents with hepatomegaly, splenomegaly and occasional lung and bone disease; this is managed, symptomatically, by enzyme replacement therapy. The acute childhood lethal form of nGD is untreatable since enzyme cannot cross the blood–brain barrier. Patients with nGD exhibit signs consistent with hindbrain neurodegeneration, including neck hyperextension, strabismus and, often, fatal apnea1. We selected a mouse model of nGD carrying a loxP-flanked neomycin disruption of Gba plus Cre recombinase regulated by the keratinocyte-specific K14 promoter. Exclusive skin expression of Gba prevents fatal neonatal dehydration. Instead, mice develop fatal neurodegeneration within 15 days2. Using this model, fetal intracranial injection of adeno-associated virus (AAV) vector reconstituted neuronal glucocerebrosidase expression. Mice lived for up to at least 18 weeks, were fertile and fully mobile. Neurodegeneration was abolished and neuroinflammation ameliorated. Neonatal intervention also rescued mice but less effectively. As the next step to clinical translation, we also demonstrated the feasibility of ultrasound-guided global AAV gene transfer to fetal macaque brains.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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Till lärosätets databas
- Av författaren/redakt...
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Massaro, Giulia
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Mattar, Citra N. ...
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Wong, Andrew M.S ...
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Sirka, Ernestas
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Buckley, Suzanne ...
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Herbert, Bronwen ...
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visa fler...
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Karlsson, Stefan
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Perocheau, Dany ...
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Burke, Derek
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Heales, Simon
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Richard-Londt, A ...
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Brandner, Sebast ...
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Huebecker, Mylen ...
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Priestman, David ...
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Platt, Frances M ...
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Mills, Kevin
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Biswas, Arijit
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Cooper, Jonathan ...
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Chan, Jerry K.Y.
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Cheng, Seng H.
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Waddington, Simo ...
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Rahim, Ahad A.
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Neurologi
- Artiklar i publikationen
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Nature Medicine
- Av lärosätet
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Lunds universitet