Celiac Disease: A Challenging Disease for Pharmaceutical Scientists

Abstract

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains that affects~1% of the white ethnic population. In the last decades, a rise in prevalence of CD has been observed that cannot be fully explained by improved diagnostics. Genetic predisposition greatly influences the susceptibility of individuals towards CD, though environmental factors also play a role. With no pharmacological treatments available, the only option to keep CD in remission is a strict and permanent exclusion of dietary gluten. Such a gluten-free diet is difficult to maintain because of gluten's omnipresence in food (e.g., additive in processed food). The development of adjuvant therapies which would permit the intake of small amounts of gluten would be desirable to improve the quality of life of patients on a glutenfree diet. Such therapies include gluten-degrading enzymes, polymeric binders, desensitizing vaccines, anti-inflammatory drugs, transglutaminase 2 inhibitors, and HLA-DQ2 blockers. However, many of these approaches pose pharmaceutical challenges with respect to drug formulation and stability, or application route and dosing interval. This perspective article discusses how pharmaceutical scientists may deal with these challenges and contribute to the implementation of novel therapeutic options for patients with CD.

Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing

“…Since dietary transgressions are relatively frequent in patients with CD, 4 5 37 a method to determine inadvertent lapses or voluntary gluten intake is a long-overdue necessity to help patients with CD manage their lives and avoid the harmful effects of gluten exposure while on a GFD. In the current study, we demonstrated the presence of GIP in patients with CD who had supposedly consumed long-term GFD (45% and 48% in children and adults, respectively).…”

“… 3 At least one-third of patients with CD do not fully adhere to a GFD. 4 5 In addition, 36% to 55% of patients who declare to fully adhere to a GFD do not achieve histological remission, probably because of inadvertent lapses in daily gluten intake. 2 5–7 …”

Oral delivery of macromolecular drugs: Where we are after almost 100 years of attempts

“…As an alternative, the administration of probiotics that secrete βgalactosidase, which is capable of lactose hydrolysis, has been proposed; however, different clinical trials in patients with lactose intolerance gave inconsistent efficacy results [45]. Oral formulations of polymer-conjugated enzymes and enzymes in enteric-coated capsules are under preclinical investigation for other pathologies such as celiac disease and phenylketonuria [4,[46][47][48][49][50].…”

Non-absorbable mesoporous silica for the development of protein sequestration therapies

“…These effects have been attained with a nonabsorbable polymeric matrix (low safety risk) that is capable of selectively binding gliadin, minimizing gut exposure and facilitating elimination. [39] Given the nature of the protein and the range of available MS particles, gliadin appears a perfect candidate for sequestration. Hyperuricemia is characterized by high concentrations of uric acid in blood.…”