Novel treatment in CD
| Treatment | Comment |
|---|---|
| Cereal genomics | The 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 acetate | Larazotide 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 inhibitors | Candidate 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 molecules | No trials yet. Regarded as unpredictable |
| Subcutaneous injection of dominant immunotoxic gliadin peptides65 | Stimulates 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 agents303 | No clinical trials performed yet |
CD, coeliac disease; HLA, human leucocyte antigen; TG2, transglutaminase 2.