Introduction: The only available effective treatment for celiac disease is strict and long-term compliance with a gluten-free diet. Dietary gluten restriction must be strict and long term, but is difficult to achieve in many cases and alternative dietary strategies have been investigated in the past few years.Areas covered: This review highlights the progress that has been made in the development of new therapeutics for CD. Detailed information of the evidence about the targets of the drugs related to their mechanisms of action is covered. The therapies are classified in five mechanisms: modification of gluten, intraluminal therapies, immunomodulation, intestinal permeability and modulation of adaptative response. The actual development phase and future approach are also described and discussed.Expert opinion: There are several limitations in each of the treatment targets related to their complications or the lack of complete response to normal gluten containing diet. The most desired therapy for celiac patients is the induction of gluten tolerance that would be curative.Therefore, it is expected that shortly, alternative or complementary tools for the treatment of gluten-free diet will be available to patients with celiac disease and will improve their quality of life.Gluten is a protein that is insoluble in both water and diluted salt solutions [9]. This protein triggers intestinal inflammation mediated by the human leucocyte antigen (HLA) system via HLA-DQ2 or DQ8 molecules. Intestinal inflammation may lead to the malabsorption of nutrients, as well as secondary iron deficiency (anemia) and osteoporosis.The only available effective treatment for CD is strict and long-term compliance with a glutenfree diet (GFD). Nonetheless, it has been shown that mucosal recovery can be lengthy.Moreover, 30%-50% of patients have persistent lesions in the intestinal mucosa and recurrent symptoms despite dietary gluten restriction (GFD-resistant CD or non-responsive CD) [10, 11].Gluten restriction requires extensive personal effort, which has psychological and social consequences and may limit full compliance [12,13]. Unintentional or deliberate noncompliance with GFD occurs in up to 50% of cases [14, 15]. In addition, approximately 1% of patients with celiac disease do not respond to GFD (refractory CD [RCD]). These patients are diagnosed mainly in adulthood after long-term exposure to gluten and are at risk of developing complications such as RCD type II (an intestinal lymphoma) or its more severe complication, enteropathy-associated T-cell lymphoma (EATL) [16, 17].
PATHOGENESIS OF CDCD develops in genetically predisposed individuals as an immune response to gluten present in certain grains (wheat, barley, and rye [18]). Although oats are considered safe for patients with CD, different oat varieties have distinct immunogenic potentials in patients with celiac disease based on the presence of toxic prolamines [19]. The immune system involves innate responses (caused by the direct toxic effects of gluten on the epithelium) and ...