#28 - 🌾 New therapies, NCGS myths, & more

Hey readers! 🌾 This week brings a fascinating mix of practical guidance for families, emerging therapies moving through trials, and research that challenges some long-held assumptions about gluten sensitivity. Whether you're navigating a new diagnosis or staying current on treatment developments, there's something here to help you make informed decisions about care.

Celiac Disease in Children: Treatment and Follow-Up provides essential guidance for families managing pediatric celiac disease. The only effective treatment remains a lifelong, 100% gluten-free diet, and starting it as soon as possible after diagnosis promotes symptom relief and intestinal healing. – Beyond Celiac

Recovery timelines vary significantly by child, making routine follow-up crucial. Most families will rely on blood tests and nutrient checks to confirm the immune response has stopped and identify any vitamin or mineral deficiencies requiring supplementation. The multidisciplinary approach matters: pediatricians, gastroenterologists, dietitians, school staff, and support groups all play vital roles in helping families manage daily life. Because celiac disease is genetic, family screening is strongly recommended.

UMass Memorial Health reinforces these fundamentals while adding practical detail. Most children begin feeling better within two to four weeks of removing gluten, with symptoms resolving completely for many within six months. The article provides helpful lists of which grains and common foods contain gluten, naturally gluten-free alternatives, and warnings about hidden sources and cross-contamination. Annual follow-up with antibody testing helps maintain control and detect accidental exposure. – UMass Memorial Health

Several promising pharmacological treatments are advancing through clinical trials, offering hope for managing accidental exposures or refractory cases.

Latiglutenase demonstrated meaningful results in a double-blind, placebo-controlled trial. The enzyme reduced gluten-induced intestinal mucosal damage and attenuated symptom severity in patients exposed to a gluten challenge. The mean change in intraepithelial lymphocyte density was 9.8 cells/mm epithelium for latiglutenase versus 24.8 for placebo, a statistically significant difference. This suggests the therapy may offer protection for individuals who experience accidental gluten exposure. – PubMed

ZED1227, a first-in-class tissue transglutaminase inhibitor, represents a different therapeutic approach. The small molecule works by selectively binding to the active state of TG2, inhibiting its activity and potentially preventing the cascade of events that lead to celiac disease symptoms. Clinical administration has validated TG2 as a "druggable" target in celiac disease, opening possibilities for broader therapeutic applications. – PubMed

TAK-062, an engineered endopeptidase, showed impressive gluten degradation capabilities in phase I trials. In vitro, the enzyme degraded more than 99% of gluten within 10 minutes. In complex meals containing one to six grams of gluten, TAK-062 achieved median gluten degradation ranging from 97% to more than 99% at 20 to 65 minutes post-dose. The enzyme was well-tolerated in both healthy participants and celiac disease patients. – PubMed

A comprehensive review of therapeutic targets predicts the first generation of pharmacologic agents for celiac disease will receive approval within the next five years. Multiple promising agents are in development, targeting various steps in the disease's pathophysiology, including peptidases, gluten sequestrants, and immune-modulating therapies. These options may serve as adjuncts to the gluten-free diet for accidental or intentional exposures, or for refractory disease. – John Wiley & Sons Ltd.

A systematic review and meta-analysis examined the global prevalence of celiac disease using data from studies published between 1991 and 2016. The pooled global prevalence based on serologic testing was 1.4%, while biopsy-confirmed prevalence was 0.7%. Prevalence varied significantly by region, sex, and age, with higher rates in females and children (0.9% versus 0.5% in adults). The authors suggest a need for further population-based studies in many countries to better understand global distribution. – Elsevier Inc.

Research into gluten T cell epitopes continues to advance our understanding of disease mechanisms. CD4+ T cells recognizing gluten epitopes presented by disease-associated HLA-DQ allotypes drive the pathogenesis of celiac disease. An updated listing of these epitopes, including their names and sequences, is vital for understanding and managing the condition. – Direct Cell Cloning

Type 2 transglutaminase plays a central role as the primary autoantigen in celiac disease. TG2 deamidates gluten peptides, increasing their immunogenicity in the intestinal mucosa. Serum antibodies against TG2 represent a valuable marker for diagnosis, and ongoing research seeks to discover specific and potent inhibitors that could be employed in new therapeutic approaches. – PubMed

A major review published in The Lancet challenges popular beliefs about non-celiac gluten sensitivity. Researchers from the University of Melbourne conclude that most self-reported NCGS is not caused by gluten itself but by fermentable carbohydrates (FODMAPs), other wheat components, and gut-brain factors such as expectations and placebo effects. – University of Melbourne

The authors argue NCGS aligns more closely with the gut-brain interaction spectrum, similar to IBS, than a standalone gluten disorder. They recommend reframing diagnosis and care toward personalized, evidence-based approaches that combine dietary modification with psychological support, improved diagnostics, and clearer public health messaging to avoid unnecessary gluten avoidance. This research has important implications for how we counsel patients and the general public about gluten-related concerns.

Several studies have examined mortality risks in celiac disease patients, with nuanced findings that reflect improvements in diagnosis and care.

A Swedish population study covering diagnoses from 1969 to 2017 found a small but statistically significant increase in overall mortality risk compared to the general population. The increased risk was present across all age groups, particularly within the first year after diagnosis, and persisted beyond ten years. Individuals with celiac disease showed increased risk of death from cardiovascular disease, cancer, and respiratory disease. – PubMed

However, Finnish research focusing on adults diagnosed between 2005 and 2014 found that overall mortality was not increased in this more recent cohort. While mortality from lymphoproliferative diseases was initially elevated, these risks decreased after excluding the first two years of follow-up. This suggests that earlier diagnosis and better management may be improving long-term outcomes. – PubMed

Research on mucosal recovery emphasizes why follow-up matters. Mucosal recovery after a gluten-free diet was not achieved in a substantial portion of adults with celiac disease, though most showed clinical improvement. The Kaplan-Meier rate of confirmed mucosal recovery was 34% at two years and 66% at five years following diagnosis. Poor compliance with the gluten-free diet, severe symptoms, and initial villous atrophy were associated with persistent mucosal damage. There was a borderline significant association between confirmed mucosal recovery and reduced mortality, independent of age and gender. – PubMed

Mayo Clinic Research is conducting numerous clinical trials investigating different aspects of celiac disease. Studies explore gut permeability, the safety and efficacy of new drug treatments, immune responses, the effects of gluten challenges, and potential antibody therapies. These trials, based primarily in Rochester, Minnesota, with some sites in Arizona and Florida, aim to improve diagnosis, treatment options, and understanding of the disease. – Mayo Clinic Research

A study on gluten-free dietary guidance found that while a gluten-free guide can improve diet quality for children, sustained positive change requires ongoing support. This underscores the importance of continued access to dietitians and support networks beyond the initial diagnosis period. – Priyanjana Pramanik, MSc.

The National Celiac Association provides comprehensive information emphasizing that celiac disease affects at least 1% of the population, with many cases remaining undiagnosed. The organization stresses the importance of strict, lifelong adherence to a gluten-free diet and regular follow-up care, including testing for associated conditions. – National Celiac Association

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