Is There a Future Without Gluten Restrictions for Celiac Patients? Update on Current Treatments

Celiac disease (CeD) is a chronic autoimmune enteropathy triggered by dietary gluten in genetically predisposed individuals. Along with other disorders such as non-celiac gluten/wheat sensitivity and gluten allergy, adherence to a strict gluten-free diet (GFD) is required as the only effective treatment for CeD. To this end, and partially due to the burdensome nature and limited efficacy in some patients of a GFD, significant research into alternative therapies has been catalyzed. This review gives a perspective on current and emerging treatment strategies targeting different aspects of CeD pathogenesis. These include gluten-degrading enzymes (e.g., AN-PEP, Latiglutenase, Zamaglutenase), gluten-sequestering agents (e.g., AGY-010, BL-7010), modulators of intestinal permeability (e.g., Larazotide acetate, IMU-856), immune-modulating agents (e.g., ZED1227, AMG 714, EQ102), and strategies for immune tolerization (e.g., TAK-101, KAN-101, Nexvax2). Newer approaches are also targeting probiotics to modulate the gut microbiota (e.g., VSL#3, Lactobacillus plantarum HEAL9), nutraceuticals (e.g., polyphenols, vitamins), or food modifications to remove the gluten from naturally gluten-containing foodstuffs (e.g., gluten transamidation, Gluten Friendly™ technology). Despite encouraging results in preclinical and clinical trials, no treatment has yet been conclusively proven to serve as an effective alternative to the GFD. Continued research is essential to validate efficacy, optimize dosing, and ensure safety in broader patient populations. Here, we provide a comprehensive overview of the therapeutic landscape for CeD, analyze the main strengths and limitations of each treatment and highlight promising directions for future management of CeD, altogether evidencing the urgent need to develop effective alternatives for these patients.