Novel Drug Therapeutics in Celiac Disease: A Pipeline Review

Varma, Sanskriti; Krishnareddy, Suneeta

doi:10.1007/s40265-022-01784-2

Cited by 9 publications

(10 citation statements)

References 103 publications

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“…So far no drugs for celiac disease treatment have been approved by the Food and Drug Administration. However, given the numerous limitations of a gluten-free diet, including cost, reduced quality of life, or lack of response to treatment with a gluten-free diet in up to 7%–30% of patients, new treatment strategies are being sought ( Varma and Krishnareddy, 2022 ).…”

Section: Celiac Disease Novel Therapiesmentioning

confidence: 99%

“…This involves the oral administration of exogenous endopeptidases that digest gluten in the intestinal lumen. This prevents gluten from reaching the lamina propria and stimulating the immune system ( Varma and Krishnareddy, 2022 ). Other proposed strategies aim at blocking immune response to gluten peptides by: • transglutaminase transglutaminase 2 (TG2) blockers preventing deamidation of gluten peptides and their efficient presentation to CD4 + T cells ( Paolella et al, 2022 ); • inhibiting epithelial damage driven by IL-15 with anti-IL15 antibodies or opposing the outgrowth of malignant IELs in type II refractory CD; • immunotherapy to restore gluten tolerance through stimulation-induced death of small intestinal epithelial cells and immune activation through the production of regulatory T cells ( Cerf-Bensussan and Schuppan, 2021 ; Varma and Krishnareddy, 2022 ).…”

Section: Celiac Disease Novel Therapiesmentioning

confidence: 99%

“…• immunotherapy to restore gluten tolerance through stimulation-induced death of small intestinal epithelial cells and immune activation through the production of regulatory T cells ( Cerf-Bensussan and Schuppan, 2021 ; Varma and Krishnareddy, 2022 ).…”

Section: Celiac Disease Novel Therapiesmentioning

confidence: 99%

“…Larazotide acetate in phase I and II studies was shown to be safe, well tolerated and to prevent worsening of gluten-induced symptom severity and to suppress serological markers. However, a placebo-controlled phase III study was terminated ( Varma and Krishnareddy, 2022 ).…”

Section: Celiac Disease Novel Therapiesmentioning

confidence: 99%

“…Moreover, novel therapies include probiotic therapy that potentially may improve gut microbiota composition and maintain gut microbiota homeostasis, digest gluten peptides into small polypeptides, and limit the availability of immunogenic polypeptides to lamina propria ( Krishnareddy, 2019 ; Varma and Krishnareddy, 2022 ). The potential benefits of probiotics in the treatment of celiac disease are presented in Figure 1 .…”

Section: Celiac Disease Novel Therapiesmentioning

confidence: 99%

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From an understanding of etiopathogenesis to novel therapies—what is new in the treatment of celiac disease?

Skoracka,

Hryhorowicz,

Tovoli

et al. 2024

Front. Pharmacol.

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Celiac disease, a chronic autoimmune disorder caused by genetic factors and exposure to gluten, is increasingly being recognized and diagnosed in both children and adults. Scientists have been searching for a cure for this disease for many years, but despite the impressive development of knowledge in this field, a gluten-free diet remains the only recommended therapy for all patients. At the same time, the increasing diagnosis of celiac disease in adults, which was considered a childhood disease in the 20th century, has opened a discussion on the etiopathology of the disease, which is proven to be very complex and involves genetic, immunological, nutritional, environmental and gut microbiota-related factors. In this review, we extensively discuss these factors and summarize the knowledge of the proposed state-of-the-art treatments for celiac disease to address the question of whether a better understanding of the etiopathogenesis of celiac disease has opened new directions for therapy.

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Section: Celiac Disease Novel Therapiesmentioning

confidence: 99%

Section: Celiac Disease Novel Therapiesmentioning

confidence: 99%

Section: Celiac Disease Novel Therapiesmentioning

confidence: 99%

Section: Celiac Disease Novel Therapiesmentioning

confidence: 99%

Section: Celiac Disease Novel Therapiesmentioning

confidence: 99%

See 3 more Smart Citations

From an understanding of etiopathogenesis to novel therapies—what is new in the treatment of celiac disease?

Skoracka,

Hryhorowicz,

Tovoli

et al. 2024

Front. Pharmacol.

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The role of tryptophan metabolism and tolerogenic dendritic cells in maintaining immune tolerance: Insights into celiac disease pathogenesis

Asgari,

Khodadoust,

Nikzamir

et al. 2024

Immunity Inflam & Disease

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BackgroundIn mammals, amino acid metabolism has evolved to control immune responses. Tryptophan (Trp) is the rarest essential amino acid found in food and its metabolism has evolved to be a primary regulatory node in the control of immune responses. Celiac disease (CeD) is a developed immunological condition caused by gluten intolerance and is linked to chronic small intestine enteropathy in genetically predisposed individuals. Dendritic cells (DCs), serving as the bridge between innate and adaptive immunities, can influence immunological responses in CeD through phenotypic alterations.ObjectiveThis review aims to highlight the connection between Trp metabolism and tolerogenic DCs, and the significance of this interaction in the pathogenesis of CeD.ResultsIt is been recognized that various DC subtypes contribute to the pathogenesis of CeD. Tolerogenic DCs, in particular, are instrumental in inducing immune tolerance, leading to T‐reg differentiation that helps maintain intestinal immune tolerance against inflammatory responses in CeD patients and those with other autoimmune disorders. T‐regs, a subset of T‐cells, play a crucial role in maintaining intestinal immunological homeostasis by regulating the activities of other immune cells. Notably, Trp metabolism, essential for T‐reg function, facilitates T‐reg differentiation through microbiota‐mediated degradation and the kynurenine pathway.ConclusionTherefore, alterations in Trp metabolism could potentially influence the immune response in CeD, affecting both the development of the disease and the persistence of symptoms despite adherence to a gluten‐free diet.

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