Novel Nondietary Therapies for Celiac Disease

Alhassan, Eaman; Yadav, Abhijeet; Kelly, Ciarán P.; Mukherjee, Rupa

doi:10.1016/j.jcmgh.2019.04.017

Cited by 50 publications

(50 citation statements)

References 59 publications

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“…The search for alternate therapeutic pathways for the treatment of CeD has become a topic of high importance for the celiac community and health care providers [30,38,39]. Food-grade proteases capable of detoxifying moderate quantities of dietary gluten (up to 3 g gluten per day in view of an average daily consumption of 15-20 g gluten) [40] could help mitigate this problem [34].…”

Section: The Approach For the Use Of Gluten-degrading Enzymes In Cedmentioning

confidence: 99%

Gluten Degrading Enzymes for Treatment of Celiac Disease

Wei¹,

Helmerhorst²,

Darwish³

et al. 2020

Nutrients

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Celiac disease (CeD) affects about 1% of most world populations. It presents a wide spectrum of clinical manifestations, ranging from minor symptoms to mild or severe malabsorption, and it may be associated with a wide variety of autoimmune diseases. CeD is triggered and maintained by the ingestion of gluten proteins from wheat and related grains. Gluten peptides that resist gastrointestinal digestion are antigenically presented to gluten specific T cells in the intestinal mucosa via HLA-DQ2 or HLA-DQ8, the necessary genetic predisposition for CeD. To date, there is no effective or approved treatment for CeD other than a strict adherence to a gluten-free diet, which is difficult to maintain in professional or social environments. Moreover, many patients with CeD have active disease despite diet adherence due to a high sensitivity to traces of gluten. Therefore, safe pharmacological treatments that complement the gluten-free diet are urgently needed. Oral enzyme therapy, employing gluten-degrading enzymes, is a promising therapeutic approach. A prerequisite is that such enzymes are active under gastro-duodenal conditions, quickly neutralize the T cell activating gluten peptides and are safe for human consumption. Several enzymes including prolyl endopeptidases, cysteine proteases and subtilisins can cleave the human digestion-resistant gluten peptides in vitro and in vivo. Examples are several prolyl endopeptidases from bacterial sources, subtilisins from Rothia bacteria that are natural oral colonizers and synthetic enzymes with optimized gluten-degrading activities. Without exception, these enzymes must cleave the otherwise unusual glutamine and proline-rich domains characteristic of antigenic gluten peptides. Moreover, they should be stable and active in both the acidic environment of the stomach and under near neutral pH in the duodenum. This review focuses on those enzymes that have been characterized and evaluated for the treatment of CeD, discussing their origin and activities, their clinical evaluation and challenges for therapeutic application. Novel developments include strategies like enteric coating and genetic modification to increase enzyme stability in the digestive tract.

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Section: The Approach For the Use Of Gluten-degrading Enzymes In Cedmentioning

confidence: 99%

Gluten Degrading Enzymes for Treatment of Celiac Disease

Wei¹,

Helmerhorst²,

Darwish³

et al. 2020

Nutrients

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show abstract

“…As such, the use of CCX282-B, a CCR9 receptor antagonist, has been considered as an alternative therapy for CD patients. A phase 2 clinical trial has been performed in CD patients following a GFD and challenged with gluten, however, the results have not been published yet (74).…”

Section: Immune Therapiesmentioning

confidence: 99%

“…While conceptually promising, the use of HLA blockers has raised several issues and pre-clinical trials have been yet to be initiated. Due to the partial agonist effect exerted by these peptides, in fact, HLA DQ2/DQ8 blockade may not be complete, therefore resulting in severe immunosuppression ( 70 , 74 ).…”

Section: Alternative/adjuvant Therapies To Gluten Free Dietmentioning

confidence: 99%

Celiac Disease and Non-celiac Wheat Sensitivity: State of Art of Non-dietary Therapies

2020

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Gluten related disorders (GRD), which include celiac disease, non-celiac wheat sensitivity and wheat allergy are heterogeneous conditions triggered by ingestion of glutencontaining grains. Together, their prevalence is estimated to be ∼5% in the general population, however, in the last years the number of diagnoses has been rapidly increasing. To this day, the gold standard treatment for these disorders is the complete removal of gluten-containing grains from the diet. Although this therapy results effective in the majority of patients, up to 30% of individuals affected by GRD continue to present persistent symptoms. In addition, gluten-free diet has been shown to have poor nutritional quality and to cause a socioeconomic burden in patients' quality of life. In order to respond to these issues, the scientific community has been focusing on finding additional and adjuvant non-dietary therapies. In this review, we focus on two main gluten related disorders, celiac disease and non-celiac wheat sensitivity. We delineate the actual knowledge about potential treatments and their relative efficacy in pre-clinical and clinical trials.

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“…These best studied to date descriptively fall into different classes (26)(27)(28), including endopeptidases (i.e., latiglutenase or ALV003, Aspergillus niger peptidase) and tight junction inhibitors (larazotide, or AT-1001). As noted (28), latiglutenase reduced gluten challenge-induced mucosal changes as well as increased numbers of intra-epithelial lymphocytes or had no effect on improving histologic scores or symptoms compared to placebo, while Aspergillus niger peptidase was not effective in preventing mucosal damage induced by 7 g gluten daily for 2 weeks.…”

Section: Studies Of Novel Investigational Agentsmentioning

confidence: 99%

Evaluation of Non-dietary Alternatives for Treatment of Adults With Celiac Disease

Freeman

2020

Front. Nutr.

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Novel Nondietary Therapies for Celiac Disease

Cited by 50 publications

References 59 publications

Gluten Degrading Enzymes for Treatment of Celiac Disease

Gluten Degrading Enzymes for Treatment of Celiac Disease

Celiac Disease and Non-celiac Wheat Sensitivity: State of Art of Non-dietary Therapies

Evaluation of Non-dietary Alternatives for Treatment of Adults With Celiac Disease

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