Prospects of Developing Medicinal Therapeutic Strategies and Pharmaceutical Design for Effective Gluten Intolerance Treatment

Abstract

Gluten intolerance is an umbrella term for gluten-related disorders manifested in health decline as a result of the gluten ingestion. The spectrum of gluten-related disorders includes three major groups: autoimmune (mainly, Celiac Disease, CD, also known as Celiac Sprue, dermatitis herpetiformis, or gluten-sensitive ataxia), allergic (wheat allergy, WA), and non-autoimmune non-allergic (non-celiac gluten sensitivity, NCGS, or gluten sensitivity, GS). Pathogenesis and diagnostics of CD and WA are well established in contrast to NCGS, pathogenicity of which is still poorly understood and its symptoms are frequently misdiagnosed since most of the NCGS cases are currently identified via the process of CD and WA exclusion. By now, the only one proven effective way for CD treatment is gluten-free diet (GFD). However, such an increasingly gaining popularity diet is apparently unsuitable for NCGS treatment because in this case gluten does not always arise as the major or exclusive culprit of gastrointestinal disorder. Furthermore, it is some physicians' opinion that GFD can be deficient in fiber and in other vitamins and minerals. In many cases, GFD is commercially inaccessible for the most needy, whereas strict adherence to the diet is complicated by the presence of small amounts of the gluten components in some foods and even medicines. In this regard, a number of research groups and pharmaceutical companies are extensively developing alternative medicinal approaches to GFD for effective gluten intolerance treatment. This review summarizes our understanding of gluten-related disorders, possible mechanisms of gluten intolerance activation and advantages of gluten intolerance medicinal treatment using novel drug candidates obtained with a proper pharmaceutical design.

Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities

“…Thus, it has been proposed that exogenous enzymes can be employed for additional enzyme supplement therapy to promote the complete digestion of cereal proteins, and thus destroy T-cell gluten epitopes, in particular [129,130]. A number of peptidases possessing glutenase activities were isolated from germinating cereals ( Hordeum vulgare L., Triticum aestivum L.), bacteria ( Flavobacterium meningosepticum , Sphingomonas capsulate , Myxococcus xanthus ), fungi ( Aspergillus niger , Aspergillus oryzae ), and stored-product pest yellow mealworm ( Tenebrio molitor ) [131,132,133,134,135]. One of them is ALV003 enzyme—modified recombinant EP-B2 enzyme from barley, and prolyl endopeptidase from bacteria Sphingomonas capsulate —was shown to be effective in vitro and in vivo, non-toxic and without allergic reactions [136,137].…”

Current Paediatric Coeliac Disease Screening Strategies and Relevance of Questionnaire Survey

“…Therefore, there are non-dietary CD treatments are in various stages of development, using exogenous gluten-degrading enzymes, substrates regulating intestinal permeability, various forms of immunotherapy, etc. [14]. …”

Overview of Celiac Disease in Russia: Regional Data and Estimated Prevalence

“…However, some cereals are an important source of proteins, lipids, vitamins, minerals, and fibre, and their inclusion in a gluten-free diet might improve the nutritional status of celiac patients but the immunogenicity of certain grain cultivars should be thoroughly tested [3, 4]. Since CD is a common and lifelong disorder, many studies have focused on the intensive development of drugs for the treatment of gluten intolerance [5]. Medical treatment will significantly improve the quality of life of patients with gluten-related diseases by allowing a nonstrict gluten-free diet.…”