Current and novel therapeutic strategies in celiac disease.
BACKGROUND
A gluten free diet (GFD) is the only available treatment for celiac disease (CD). However many patients fail to respond fully clinically or histologically. Several surveys highlight the psychosocial implications of adherence to a GFD. Hence, efforts are ongoing to develop therapeutic strategies beyond a GFD.


METHODS
We conducted a search of PubMed and clinicaltrials.gov to extract articles on CD using keywords including 'celiac disease' and 'refractory celiac disease' (RCD) and focused on articles conducting pathophysiologic and therapeutic research in/ex-vivo models and human trials. We highlight novel therapeutics that manipulate these mechanisms including tight junction regulators, glutenases, gluten sequestrants and immunotherapy using vaccines, nanoparticles that may serve as adjuncts to a GFD or more ambitiously to allow for gluten consumption. We also highlight the role of anti-inflammatories, immunosuppressants and monoclonal antibodies in RCD. Expert commentary: Therapeutics including tight junction regulators, glutenases have the potential to be approved for non-responsive CD or as gluten adjuncts. We expect results of various phase 1/2 trials using AMG 714, BL 7010, IgY antibodies to be published. In the interim, off-label use of 5 amino-salicylates, budesonide, nucleoside analogues and newer biologics developed for other inflammatory diseases will be used in RCD.
a Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , MA , USA.|b Department of Medicine, Boston Medical Center , Boston University School of Medicine , Boston , MA , USA.|c Celiac Research Program, Harvard Medical School , Boston , MA , USA.
Satya
S
Kurada
a Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , MA , USA.|c Celiac Research Program, Harvard Medical School , Boston , MA , USA.
Abhijeet
A
Yadav
a Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , MA , USA.|c Celiac Research Program, Harvard Medical School , Boston , MA , USA.
Daniel A
DA
Leffler
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002446:Celiac Disease / Q000503:physiopathology / Q000628:therapy*; D055050:Diet, Gluten-Free; D015195:Drug Design; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods; D056687:Off-Label Use; D010349:Patient Compliance
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents
Celiac disease; gluten free diet; glutenase; larazotide; refractory celiac disease; tight junction regulators