Journal article
Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C
Wellcome open research, Vol.7, pp.11-11
01/11/2022
DOI: 10.12688/wellcomeopenres.16986.1
PMCID: PMC9171292
PMID: 35694196
Abstract
Background:
Blockade of tumour necrosis factor (anti-TNF) is effective in patients with Crohn’s Disease but has been associated with infection risk and neurological complications such as demyelination. Niemann-Pick disease Type C1 (NPC1) is a lysosomal storage disorder presenting in childhood with neurological deterioration, liver damage and respiratory infections. Some NPC1 patients develop severe Crohn’s disease. Our objective was to investigate the safety and effectiveness of anti-TNF in NPC1 patients with Crohn’s disease.
Methods:
Retrospective data on phenotype and therapy response were collected in 2019-2020 for the time period 2014 to 2020 from patients in the UK, France, Germany and Canada with genetically confirmed NPC1 defects and intestinal inflammation. We investigated TNF secretion in peripheral blood mononuclear cells treated with NPC1 inhibitor in response to bacterial stimuli
.
Results:
NPC1 inhibitor treated
peripheral blood mononuclear cells (PBMCs) show significantly increased TNF production after lipopolysaccharide or bacterial challenge providing a rationale for anti-TNF therapy. We identified 4 NPC1 patients with Crohn’s disease (CD)-like intestinal inflammation treated using anti-TNF therapy (mean age of onset 8.1 years, mean treatment length 27.75 months, overall treatment period 9.25 patient years). Anti-TNF therapy was associated with reduced gastrointestinal symptoms with no apparent adverse neurological events. Therapy improved intestinal inflammation in 4 patients.
Conclusions:
Anti-TNF therapy appears safe in patients with NPC1 and is an effective treatment strategy for the management of intestinal inflammation in these patients.
Details
- Title: Subtitle
- Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C
- Creators
- Isabelle Williams - University of OxfordSumeet Pandey - University of OxfordWolfram Haller - Birmingham Children's HospitalHien Quoc Huynh - University of AlbertaAlicia Chan - Stollery Children's HospitalGesche Düeker - University Hospital BonnRuth Bettels - University Hospital MünsterLaurent Peyrin-Biroulet - Université de LorraineChinenye R. Dike - University of IowaCatherine DeGeeter - University of IowaDavid Smith - University of OxfordNada Al Eisa - King Saud bin Abdulaziz University for Health SciencesNick Platt - University of OxfordThorsten Marquardt - University Hospital MünsterTobias Schwerd - Department of Paediatrics, Dr. von Hauner Children’s Hospital, Munich, GermanyFrances M. Platt - University of OxfordHolm H. Uhlig - University of Oxford
- Resource Type
- Journal article
- Publication Details
- Wellcome open research, Vol.7, pp.11-11
- DOI
- 10.12688/wellcomeopenres.16986.1
- PMID
- 35694196
- PMCID
- PMC9171292
- NLM abbreviation
- Wellcome Open Res
- ISSN
- 2398-502X
- eISSN
- 2398-502X
- Publisher
- F1000 Research Limited
- Grant note
- Ministry of Education – Kingdom of Saudi Arabi Deutsche Forschungsgemeinschaft King Saud bin Abdulaziz University for Health Science WolfsonResearchMeritAward / Royal Society Health Research (NIHR) Oxford Biomedical Research Centre 202834 / Wellcome 11/YH/0020; 16/YH/024 / Oxford GI Biobank Leona M. and Harry B. Helmsley Charitable Trust National Institute for Health Research Ministry of National Guard Health Affairs King Abdulaziz Medical City
- Language
- English
- Date published
- 01/11/2022
- Academic Unit
- Stead Family Department of Pediatrics; Gastroenterology, Hepatology, Pancreatology, and Nutrition
- Record Identifier
- 9984353802902771
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