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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: 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. 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. 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 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

Celiac.com 08/17/2023 - KAN-101, the most recent drug designed to induce immune tolerance to wheat gluten, has proven safe and tolerable in the Phase 1 stage of testing. Now the hard work starts. The drug has shown promise for treating celiac disease, an autoimmune condition where the body reacts negatively to gluten in the small intestines. The drug, developed by Anokion, targets the liver to promote immune tolerance to gluten in people with celiac disease. KAN-101 Demonstrated Safety and Pharmacokinetic Potential In the first-in-human phase 1 ACeD trial, KAN-101 demonstrated safety and pharmacokinetic potential. The trial involved 41 adult patients with biopsy-confirmed celiac disease, all with the HLA-DQ2.5 genotype, which is associated with celiac disease. The patients received different doses of KAN-101 through intravenous administration. No Serious Adverse Events or Dose-limiting Toxicities Results showed that the drug had acceptable safety, with no serious adverse events or dose-limiting toxicities. Common mild to moderate side effects included nausea, diarrhea, abdominal pain, and vomiting, which were consistent with celiac disease symptoms. KAN-101 rapidly cleared from the patients' systems within approximately 6 hours, and there was no accumulation on repeated dosing. Deborah Geraghty, CEO of Anokion, expressed excitement about the drug's potential to induce immune tolerance to gluten, providing a durable treatment effect for celiac disease patients. With celiac disease currently lacking an FDA-approved treatment option, KAN-101 could be a game-changer. The research team plans to further analyze KAN-101's efficacy and safety in human patients, particularly with biomarker responses from a gluten challenge, at doses of 0.6 mg/kg or higher in those with celiac disease. If successful, KAN-101 could significantly impact the lives of those with celiac disease by providing a viable and effective treatment option. While the early testing is encouraging, it's a long haul from Phase 1 to full approval, and so far, no drug designed to treat celiac disease has made the journey. The failures are legion. So, celiac sufferers should take this news with a grain of salt. Read more at HCPlive.com

Celiac.com 07/26/2022 - Previous drugs designed to induce tolerance to gliadin have met with failure. Will the latest effort fare any better? In people with celiac disease, gliadin-specific T cells drive an adverse immune response to gluten peptides, which can cause symptoms, long-term gut damage, and other related conditions. Currently, the only treatment for celiac disease is a gluten-free diet. A new drug, KAN-101, designed to treat celiac disease by inhibiting a key celiac disease biomarker, has received fast track status from the FDA ahead of Phase 2 Trials slated for the second half 2022. Designed by Anokion SA, a clinical-stage biotechnology company focused on treating autoimmune disease by restoring normal immune tolerance, KAN-101 has been found to be safe, well-tolerated, and to provide the proper immune responses. KAN-101 is designed to induce tolerance to gliadin, a core component of gluten, through natural pathways in the liver. The Phase 1, randomized, double-blind, placebo-controlled trial enrolled a total of 41 individuals with celiac disease on a gluten-free diet in both single-ascending dose (SAD) and multi-ascending dose (MAD) cohorts. Findings from the Phase 1 trial showed that treatment with KAN-101 was safe and tolerated, and successfully reduced T cell responses following gluten challenge. The primary endpoint of the Phase 1 trial is to assess the safety and tolerability of KAN-101, with secondary endpoints to assess KAN-101 serum concentrations and pharmacokinetics. Additional end points include the assessment of cytokines critical to both innate and adaptive immunity, T cell responses, and other serum cytokines and celiac disease symptoms. Patients who recieved KAN-101 experienced dose-dependent reductions of gluten-induced plasma IL-2, a cytokine that is elevated in celiac patients after gluten ingestion, and which reflects severity of acute symptoms. Patients who received the 0.6mg/kg dose experienced statistically significant reductions of IL-2, compared to other groups Administration of KAN-101 did not increase gut-homing CD8 T cell responses after gluten challenge, an indicator of immune response to gluten exposure in patients with celiac disease. Stories about new drugs designed to induce tolerance to gluten always cause great excitement within the celiac disease community. However, previous drugs designed to induce tolerance to gliadin have met with failure. Will the latest effort fare any better? Stay tuned for more as KAN-101 moves into its Phase 2 trial later this year. Read more at Businesswire.com