Innovative Treatments for Celiac Disease in Development

Celiac.com 06/29/2024 - Celiac disease is an autoimmune disorder where ingesting gluten leads to damage in the small intestine for those genetically predisposed. The standard treatment for celiac disease is a strict gluten-free diet, which, while effective, can be challenging to maintain and does not always completely prevent symptoms or intestinal damage. This has led researchers to explore new therapeutic approaches aimed at improving the lives of those with celiac disease. These novel therapies fall into five main categories: modulating the immune response to gluten, eliminating gluten before it reaches the intestine, inducing gluten tolerance, modulating intestinal permeability, and restoring a healthy gut microbiota.

Modulating the Immune Response

One promising area of research involves therapies that block the presentation of gluten peptides by HLA-DQ2 and HLA-DQ8, which are gene variants strongly associated with celiac disease. Three therapies in this category show significant promise:

1. TPM502: This therapy uses three gluten-specific antigenic peptides that interact with T-cells associated with the HLA-DQ2.5 gene. A Phase 2a clinical trial is evaluating the safety and effects of TPM502 in adults with celiac disease. This trial is randomized, placebo-controlled, and involves multiple centers. Patients receive two infusions of TPM502 or a placebo, with the dose escalating through four cohorts to determine the optimal dosage. The study aims to monitor safety, tolerability, and pharmacodynamics.
2. KAN-101: Designed to induce gluten tolerance, KAN-101 targets specific receptors in the liver. The study for KAN-101 is a three-part trial that includes an open-label, multiple ascending dose phase, followed by two double-blind, placebo-controlled phases. Part A of the study assesses the safety and tolerability of KAN-101, while Parts B and C focus on the response to gluten challenges and biomarker responses. This therapy has received Fast Track designation by the US Food and Drug Administration, highlighting its potential to address unmet needs in celiac disease treatment.
3. DONQ52: This is a multi-specific antibody targeting HLA-DQ2. The ongoing clinical trial for DONQ52 involves two parts: a single ascending dose phase and a multiple ascending dose phase, both designed to evaluate the safety and tolerability of the drug in patients with well-controlled celiac disease. This trial aims to understand how the drug behaves in the body and its impact on biomarkers related to celiac disease.

Eliminating Gluten Before It Reaches the Intestine

Celiac.com Sponsor (A12):
Another approach is to prevent gluten from reaching the small intestine, thereby avoiding the immune response altogether. This strategy involves enzymes that break down gluten peptides in the stomach before they can cause harm. While specific therapies in this category are not detailed in the study, the concept is based on reducing the exposure of the small intestine to gluten, thereby preventing the autoimmune reaction.

Inducing Gluten Tolerance

Inducing gluten tolerance aims to retrain the immune system to tolerate gluten without triggering an autoimmune response. KAN-101 is a notable example in this category, as it seeks to create immune tolerance by targeting receptors in the liver. This approach could potentially allow people with celiac disease to consume gluten without adverse effects.

Modulating Intestinal Permeability

Celiac disease often increases the permeability of the intestinal lining, allowing gluten peptides to enter the bloodstream and trigger an immune response. Therapies that modulate intestinal permeability aim to strengthen the intestinal barrier. By doing so, these treatments can prevent gluten peptides from passing through the intestinal wall and reduce the overall immune response.

Restoring Gut Microbiota Balance

The gut microbiota plays a crucial role in overall health and immune function. In people with celiac disease, the balance of gut bacteria is often disrupted. Therapies in this category aim to restore a healthy balance of gut microbiota, which could help reduce symptoms and improve gut health. This approach includes the use of probiotics and other microbiota-modulating treatments.

Conclusion

The development of novel therapies for celiac disease offers hope for improved management and quality of life for those affected. These therapies, which range from immune modulation to restoring gut microbiota, are still in various stages of clinical trials but show promise in addressing the limitations of a gluten-free diet. For individuals with celiac disease, these advances could mean more effective treatment options and a better ability to manage their condition without the strict dietary restrictions currently required. The ongoing research and clinical trials are a crucial step toward finding more comprehensive solutions for celiac disease, potentially transforming the standard of care in the near future.

Read more at:

• medscape.com 

• sciencedirect.com

• nature.com