Imperial College London
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ProfessorNagyHabib

Faculty of Medicine, Department of Surgery & Cancer

Professor of Hepatobiliary Surgery
 
 
 
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Contact

 

+44 (0)20 3313 8574nagy.habib

 
 
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Assistant

 

Mrs Benita White +44 (0)7960 986 387

 
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Location

 

BN1/18 B BlockHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Reebye:2018:10.1038/s41388-018-0126-2,
author = {Reebye, V and Huang, K-W and Lin, V and Jarvis, S and Cutilas, P and Dorman, S and Ciriello, S and Andrikakou, P and Voutila, J and Saetrom, P and Mintz, PJ and Reccia, I and Rossi, JJ and Huber, H and Habib, R and Kostomitsopoulos, N and Blakey, DC and Habib, NA},
doi = {10.1038/s41388-018-0126-2},
journal = {Oncogene},
pages = {3216--3228},
title = {Gene activation of CEBPA using saRNA: preclinical studies of the first in human saRNA drug candidate for liver cancer},
url = {http://dx.doi.org/10.1038/s41388-018-0126-2},
volume = {37},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Liver diseases are a growing epidemic worldwide. If unresolved, liver fibrosis develops and can lead to cirrhosis and clinical decompensation. Around 5% of cirrhotic liver diseased patients develop hepatocellular carcinoma (HCC), which in its advanced stages has limited therapeutic options and negative survival outcomes. CEPBA is a master regulator of hepatic function where its expression is known to be suppressed in many forms of liver disease including HCC. Injection of MTL-CEBPA, a small activating RNA oligonucleotide therapy (CEBPA-51) formulated in liposomal nanoparticles (NOV340- SMARTICLES) upregulates hepatic CEBPA expression. Here we show how MTL-CEBPA therapy promotes disease reversal in rodent models of cirrhosis, fibrosis, hepatosteatosis, and significantly reduces tumor burden in cirrhotic HCC. Restoration of liver function markers were observed in a carbon-tetrachloride-induced rat model of fibrosis following 2 weeks of MTL-CEBPA therapy. At 14 weeks, animals showed reduction in ascites and enhanced survival rates. MTL-CEBPA reversed changes associated with hepatosteatosis in non-alcoholic methionine and cholic-deficient diet-induced steaotic liver disease. In diethylnitrosamine induced cirrhotic HCC rats, MTL-CEBPA treatment led to a significant reduction in tumor burden. The data included here and the rapid adoption of MTL-CEBPA into a Phase 1 study may lead to new therapeutic oligonucleotides for undruggable diseases.
AU  - Reebye,V
AU  - Huang,K-W
AU  - Lin,V
AU  - Jarvis,S
AU  - Cutilas,P
AU  - Dorman,S
AU  - Ciriello,S
AU  - Andrikakou,P
AU  - Voutila,J
AU  - Saetrom,P
AU  - Mintz,PJ
AU  - Reccia,I
AU  - Rossi,JJ
AU  - Huber,H
AU  - Habib,R
AU  - Kostomitsopoulos,N
AU  - Blakey,DC
AU  - Habib,NA
DO  - 10.1038/s41388-018-0126-2
EP  - 3228
PY  - 2018///
SN  - 0950-9232
SP  - 3216
TI  - Gene activation of CEBPA using saRNA: preclinical studies of the first in human saRNA drug candidate for liver cancer
T2  - Oncogene
UR  - http://dx.doi.org/10.1038/s41388-018-0126-2
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29511346
UR  - http://hdl.handle.net/10044/1/58278
VL  - 37
ER  -
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