Imperial College London
Alternate

ProfessorEricAlton

Faculty of Medicine, National Heart & Lung Institute

Chair in Gene Therapy
 
 
 
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Contact

 

+44 (0)20 7594 7929e.alton

 
 
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Assistant

 

Miss Samia Soussi +44 (0)20 7594 7980

 
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Location

 

Emmanuel Kaye BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@inproceedings{Bell:2019:10.1089/hum.2019.29087.abstracts,
author = {Bell, RV and McKinnon, TAJ and Alton, EWFW and Griesenbach, U},
doi = {10.1089/hum.2019.29087.abstracts},
pages = {A14--A14},
publisher = {Mary Ann Liebert},
title = {Gene therapy for thrombotic thrombocytopaenic purpura},
url = {http://dx.doi.org/10.1089/hum.2019.29087.abstracts},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - CPAPER
AB  - Thrombotic Thrombocytopaenic Purpura (TTP) is a rare (∼1/200,000 people) but lifethreatening disease caused by inherited or acquired deficiencies in ADAMTS13; a metalloprotease responsible for cleavage of large von Willebrand factor (VWF) multimers in the plasma. Reduced cleavage of thrombogenic VWF multimers through deficient ADAMTS13 can lead to spontaneous, widespread accumulation of plateletrich thrombi. Without treatment, thrombi accumulation within the microvasculature causes organ failure and death in 90% of acute events. Individuals with TTP receive regular plasma infusions to restore ADAMTS13 levels. Despite current treatments reducing mortality rates, high treatment burden and morbidity associated with donorderived plasma warrants the development of a novel therapy for TTP. Gene therapy offers an alternative treatment which could prevent the onset of lifethreatening acute TTP episodes. The UK Cystic Fibrosis Gene Therapy Consortium, has developed a lentivirus pseudotyped with the Sendai virus envelope proteins F and HN for efficient lung gene transfer. Here, we assess whether lungs can be used as ‘factories’ for efficient and persistent ADAMTS13 production. We first cloned ADAMTS13 cDNA into a lentivirus producer plasmid and demonstrated proteolytic activity against VWF following coexpression in HEK293T cells and subsequent detection of cleaved VWF by SDSPAGE. Vector is currently being manufactured using GMPcompliant production methods. Next, ADAMTS13 knockout mice were characterised to determine suitable biomarkers (e.g. ADAMTS13 plasma levels and VWF cleavage activity) for assessing efficacy of pulmonary gene transfer. Future work will assess the restoration of plasma ADAMTS13 function in knockout mice and protection against TTPlike symptoms.
AU  - Bell,RV
AU  - McKinnon,TAJ
AU  - Alton,EWFW
AU  - Griesenbach,U
DO  - 10.1089/hum.2019.29087.abstracts
EP  - 14
PB  - Mary Ann Liebert
PY  - 2019///
SN  - 1043-0342
SP  - 14
TI  - Gene therapy for thrombotic thrombocytopaenic purpura
UR  - http://dx.doi.org/10.1089/hum.2019.29087.abstracts
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000481913400040&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/78830
ER  -
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