Table 1.
Summary of strategies for CD grouped according to their goals.
| Strategy | Goal | Therapy | References | |
|---|---|---|---|---|
| Removal of toxic gluten peptides before reaching the intestine | Genetic modification of gluten-containing cereals | Genetically modified wheat flours | [59,60,61] | |
| Microbial gluten modification | Pretreatment with probiotic bacteria of the genus Lactobacillus (VSL#3) | [62] | ||
| Pretreatment with microbial transglutaminase (m-TG) and N-methyl-lysine | [63] | |||
| Masking of antigenic gluten capacity | Polymeric resins HEMA-co-SS | [64,65] | ||
| AGY-010 | [66] | |||
| Luminal gluten detoxification | Prolyl endopeptidases (PEPs) | Flavobacterium meningosepticum (FM-PEP) | [67,68] | |
| Myxococcus xanthus (MX-PEP) | [69] | |||
| Sphingomonas capsulata (SC-PEP) | [70,71] | |||
| Aspergillus niger (AN-PEP) | [72] | |||
| Gluten hydrolytic enzyme cocktail | SC-PEP and EPB-2 (ALV003) | [73] | ||
| FM-PEP and EPB-2 | [74] | |||
| Subtilisin derived from Rothia mucilaginosa (Sub-A) | [75] | |||
| Cysteine endopeptidase derived from Hordeum vulgare (EP-B2) | [21] | |||
| Elastase derived from Homo sapiens (CEL-3B) | [22] | |||
| Regulation of the immunostimulatory effects of toxic gluten peptides | Immune response regulation | Inhibition of transglutaminase (ZED 1227) | [76] | |
| Blocker of HLA DQ binding to T-cells | [77] | |||
| NK lymphocyte activation blocker: NKG2D receptor antagonists | [78] | |||
| Lymphocyte recruitment blocker | Anti-α4 integrin (natalizumab) | [79] | ||
| Anti-integrin α4β7 (vedolizumab) | ||||
| Binding inhibitors CD40-CD40L | ||||
| Binding inhibitors CXCL10- CXCR3 | ||||
| Binding inhibitors CCL25-CCR9 | ||||
| Anti-cytokines | Anti-IL-15, PRV-015, CALY-002 (AMG714) | [76,80] | ||
| Anti-TNF-α (infliximab and adalimumab) | ||||
| Anti-TNF- γ (fontolizumab) | ||||
| Inhibition of the proinflammatory cascade | Anti-inflammatories (generic corticosteroids, budesonide, mesalazine) | [81] | ||
| Modulation of intestinal permeability | Barrier enhancing therapies | Larazotide acetate (AT-1001 and INN-202) | [82,83] | |
| Immune modulation and induction of tolerance to gluten | Immunomodulation and gluten tolerance | Vaccine Nexvax2 | [84,85] | |
| TAK-101 (CNP-101 and TIMP-GLIA) | [86] | |||
| KAN-101 | [87] | |||
| Hookworm infection (Necator americanus) | [88] | |||
| Mucosal tolerance due to genetic modification | [89] | |||
| Restoration of the imbalance in the gut microbiota | Probiotic supplementation | Microbial therapies | [90,91] | |
TNF, tumor necrosis factor; IgA, immunoglobulin A; Il-15, interleukin 15; NK, natural killer; PEP, prolyl endopeptidase; P-HEMA-co-SS, poly-hydroxyethylmethacrylateco-styrene sulfonate.