Table 5

Novel treatment in CD

Cereal genomicsThe high copy numbers in gliadin genes have so far limited attempts to genetically modify cultivars incapable of expressing immunotoxic peptides292
RNA interference of protein translation may reduce gliadin expression, with evidence of reduced proliferation of lymphocytes challenged in vitro293
Prolyl endopeptidases (PEPs)These endopeptidases have been isolated from microbial sources and may be capable of enzymatic cleavage of the immunotoxic gluten peptides ex vivo.294 295 296 A combination of a glutamine-specific endoprotease (EP-B2 from barley) and a prolyl endopeptidase (subcutaneous PEP from Sphingomonas capsulata)297 acts synergistically and has been evaluated in a 6-week phase IIA clinical trial against 2 g gluten taken daily298
Larazotide acetateLarazotide is a tight junction regulator299 and maintains intestinal barrier function after gluten challenge.299 300 Phase IIA clinical trials have demonstrated limited effects on intestinal permeability after gluten ingestion, but beneficial effects on symptoms and signs.301
TG2 inhibitorsCandidate peptidomimetic blockers are currently entering clinical trials but no data are available yet.302 A potential limitation of this drug candidate is that TG2 activity occurs in a number of diseases and a TG2 inhibitor may therefore have unwanted side effects
Blocking of the antigen presenting groove of HLA-DQ moleculesNo trials yet. Regarded as unpredictable
Subcutaneous injection of dominant immunotoxic gliadin peptides65Stimulates an immunoregulatory T-cell response or deplete or anergise antigen specific memory T cells. Responses would be specific to the HLA haplotype DQ2 or 8. Ongoing phase II trials.
Polymer binding agents303No clinical trials performed yet
  • CD, coeliac disease; HLA, human leucocyte antigen; TG2, transglutaminase 2.