Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C
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.
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BibTeX
@article{williams2026antitnf,
title = {{Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C}},
author = {Isabelle Williams and Sumeet Pandey and Wolfram Haller and Hien Quoc Huynh and Alicia Chan and Gesche Düeker and Ruth Bettels and Laurent Peyrin‐biroulet and Chinenye Dike and Catherine Degeeter and David Smith and Nada Al Eisa and Nick Platt and Thorsten Marquardt and Tobias Schwerd and Frances Platt and Holm Uhlig},
journal = {Wellcome Open Research},
year = {2026},
month = sep,
doi = {10.12688/wellcomeopenres.16986.1},
url = {https://hal.univ-lorraine.fr/hal-04168222v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C
AU - Isabelle Williams
AU - Sumeet Pandey
AU - Wolfram Haller
AU - Hien Quoc Huynh
AU - Alicia Chan
AU - Gesche Düeker
AU - Ruth Bettels
AU - Laurent Peyrin‐biroulet
AU - Chinenye Dike
AU - Catherine Degeeter
AU - David Smith
AU - Nada Al Eisa
AU - Nick Platt
AU - Thorsten Marquardt
AU - Tobias Schwerd
AU - Frances Platt
AU - Holm Uhlig
PY - 2026
DA - 2026/09/17
JO - Wellcome Open Research
DO - 10.12688/wellcomeopenres.16986.1
UR - https://hal.univ-lorraine.fr/hal-04168222v1
AB - 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.
SN - 2398-502X
ER -