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Los Angeles Times
01-05-2025
- Health
- Los Angeles Times
How Celiac Disease Affects the Body, and How to Manage It
Celiac disease is a serious autoimmune disorder that begins with something as small as a crumb of bread. Triggered by gluten—a protein found in wheat, barley, and rye—it causes the immune system to attack the small intestine, leading to inflammation and long-term complications if left untreated. This condition only develops in people with specific genetic markers (HLA DQ2 or DQ8) [1]. Although celiac disease affects 0.5% to 2% of the global population, it often remains undiagnosed, especially outside of Western countries [2]. In celiac disease, the immune system mistakes gluten for a threat and mounts an attack that damages the small intestine. This response causes villus atrophy, where the tiny finger-like projections (villi) responsible for nutrient absorption shrink and flatten [5], [7]. The result? Poor absorption of nutrients, which can lead to fatigue, digestive distress, anemia, and more. The only treatment is a strict gluten-free diet. With careful planning and label-reading, people with celiac disease can manage their symptoms and prevent complications. You need to carry the HLA DQ2 or DQ8 genes to develop celiac disease [3], [13], but not everyone with these genes gets sick. Think of these genes as the 'key'—they open the door, but you still have to walk through it. These genetic markers are also linked to other autoimmune disorders, increasing the risk of overlapping conditions. When gluten is consumed, the immune system produces inflammatory cells and antibodies that attack the intestinal lining. This ongoing inflammation impairs digestion and can lead to widespread issues, including bone weakness and nutrient deficiencies. The World Journal of Gastrointestinal Pathophysiology notes, 'villous atrophy fundamentally disrupts normal digestion and absorption, resulting in multi-organ impacts' [7]. Celiac disease doesn't look the same for everyone. Symptoms can be obvious or silent: Digestive symptoms may include: Non-digestive symptoms might include: Some people have no gut issues at all, but still suffer internal damage. That's why antibody testing—like the anti-tissue transglutaminase (anti-tTG) test—is vital for diagnosis [4], [6], [8]. American Family Physician explains that 'serologic testing has revolutionized early detection, even in minimally symptomatic patients' [8]. Diagnosis involves a multi-step process: The American Journal of Gastroenterology notes, 'genetic testing is particularly valuable when the diagnosis remains uncertain' [13]. Untreated celiac disease can lead to: Celiac disease is also linked with other autoimmune disorders like type 1 diabetes and rheumatoid arthritis. Some patients may develop refractory celiac disease, where symptoms persist despite a gluten-free diet. Others may experience conditions like lactose intolerance or irritable bowel syndrome as coexisting issues. [9] There's no cure—just one proven treatment: a strict, lifelong gluten-free diet [6], [10], [11]. This means: Most people feel better within weeks, though full healing may take months or years depending on severity and age at diagnosis [5]. Regular check-ups and guidance from a dietitian can help ensure nutritional balance. American Family Physician states, 'patients benefit from ongoing nutritional counseling to optimize long-term outcomes' [6]. Gluten is found in: Reading labels is critical. Avoiding even trace amounts of gluten is essential to prevent symptoms and long-term damage. Dining out can be tricky, but not impossible. Many restaurants now offer gluten-free options. Ask about preparation methods and cross-contamination risks. Carry a gluten-free dining card to help explain your needs. With planning, eating out can still be safe and enjoyable. Having celiac disease raises the risk of developing other autoimmune disorders like autoimmune thyroid disease and type 1 diabetes. This is due to shared genetic and immune system triggers. Managing celiac disease with a gluten-free diet not only improves gut health but may help reduce systemic inflammation and lower the risk of additional autoimmune issues. Celiac disease is a genetic autoimmune condition that causes intestinal and systemic damage when gluten is consumed. Its symptoms vary widely—from digestive problems to silent nutrient deficiencies—but the path forward is clear: early diagnosis, followed by lifelong gluten avoidance. With commitment and proper medical guidance, people with celiac disease can lead healthy, vibrant lives. [1] Lindfors, K., Ciacci, C., Kurppa, K., Lundin, K. E. A., Makharia, G. K., Mearin, M. L., Murray, J. A., Verdu, E. F., & Kaukinen, K. (2019). Coeliac disease. Nature reviews. Disease primers, 5(1), 3. [2] Catassi, C., Verdu, E. F., Bai, J. C., & Lionetti, E. (2022). Coeliac disease. Lancet (London, England), 399(10344), 2413–2426. [3] D'Avino, P., Serena, G., Kenyon, V., & Fasano, A. (2021). An updated overview on celiac disease: from immuno-pathogenesis and immuno-genetics to therapeutic implications. Expert review of clinical immunology, 17(3), 269–284. [4] Green, P. H., Lebwohl, B., & Greywoode, R. (2015). Celiac disease. The Journal of allergy and clinical immunology, 135(5), 1099–1107. [5] Rubin, J. E., & Crowe, S. E. (2020). Celiac Disease. Annals of internal medicine, 172(1), ITC1–ITC16. [6] Pelkowski, T. D., & Viera, A. J. (2014). Celiac disease: diagnosis and management. American family physician, 89(2), 99–105. [7] Parzanese, I., Qehajaj, D., Patrinicola, F., Aralica, M., Chiriva-Internati, M., Stifter, S., Elli, L., & Grizzi, F. (2017). Celiac disease: From pathophysiology to treatment. World journal of gastrointestinal pathophysiology, 8(2), 27–38. [8] Williams, P. M., Harris, L. M., DO, & Odom, M. R. (2022). Celiac Disease: Common Questions and Answers. American family physician, 106(1), 36–43. [9] Lebwohl, B., Ludvigsson, J. F., & Green, P. H. (2015). Celiac disease and non-celiac gluten sensitivity. BMJ (Clinical research ed.), 351, h4347. [10] Selimoğlu, M. A., & Karabiber, H. (2010). Celiac disease: prevention and treatment. Journal of clinical gastroenterology, 44(1), 4–8. [11] Leonard, M. M., Sapone, A., Catassi, C., & Fasano, A. (2017). Celiac Disease and Nonceliac Gluten Sensitivity: A Review. JAMA, 318(7), 647–656. [12] Villanacci, V., Vanoli, A., Leoncini, G., Arpa, G., Salviato, T., Bonetti, L. R., Baronchelli, C., Saragoni, L., & Parente, P. (2020). Celiac disease: histology-differential diagnosis-complications. A practical approach. Pathologica, 112(3), 186–196. [13] Brown, N. K., Guandalini, S., Semrad, C., & Kupfer, S. S. (2019). A Clinician's Guide to Celiac Disease HLA Genetics. The American journal of gastroenterology, 114(10), 1587–1592.
Yahoo
06-03-2025
- Health
- Yahoo
Adiso Therapeutics Announces Data Publication of Two Phase 1 Studies of First-in-Class Neutrophil Modulator ADS051 in the American Journal of Gastroenterology
ADS051 is the first and only MRP2 / FPR1 inhibitor to demonstrate favorable safety and tolerability with signals of clinical efficacy with relief from disruptive symptoms of inflammatory bowel disease in a multiple ascending dose (MAD) study of moderately to severely active Ulcerative Colitis (UC) patients in relapse ADS051 was demonstrated to be safe in a single ascending dose (SAD) study in healthy volunteers across five dosing cohorts CONCORD, Mass., March 6, 2025 /PRNewswire/ -- Adiso Therapeutics, Inc. announced the publication of the results of two Phase 1 studies, which showed that healthy subjects and ulcerative colitis (UC) patients given oral doses of ADS051, a novel modulator of neutrophils being developed for Inflammatory Bowel Disease (IBD), could be safely administered and well-tolerated in IBD patients. These studies showed consistent safety and tolerability of ADS051 with highly encouraging signals of clinical response as determined by Mayo Endoscopic Scoring blinded to the investigator. Data from the two trials has been published in the American Journal of Gastroenterology, the official journal of the American College of Gastroenterology (ACG). The first of the two publications presents the results from the single ascending dose (SAD) trial of ADS051. This trial was the intensive first in human study of ADS051 across five (5) dosing cohorts of healthy subjects and included a deep-reaching pharmacokinetic analysis of this first and only modulator of neutrophils. There were no dose-limiting toxicities, serious adverse events (AEs), or trial discontinuation due to AEs. Pharmacokinetic data demonstrated minimal systemic absorption of ADS051, with the majority of drug excreted in the stool as expected. There was no clinical evidence of adverse immunosuppressive activity. The second publication presents the results of a multiple ascending dose (MAD) study of ADS051 in patients with moderately to severely active UC. The MAD study included three (3) placebo controlled dosing cohorts, measuring signals of clinical response using assessments typical for later stage studies, such as Mayo Endoscopic Scoring which included Clinical Remission (CR), Endoscopic Improvement (EI), and Endoscopic Response (ER). The study also looked at neutrophil-related markers of inflammation and histologic assessment. As detailed in the publication, this study achieved its primary endpoint of safety and tolerability with encouraging signs of efficacy across multiple outcome measures. "The SAD publication documents the successful completion of a very important first step in establishing patient safety. The completion of the study provided an understanding and foundation for safe dosing of ADS051 prior to exposure in patients with IBD," said Adam Cheifetz, M.D., Director, Center for Inflammatory Bowel Disease, Beth Israel Lahey Health, Beth Israel Deaconess Medical Center, Harvard Medical School Teaching Hospital. "UC is an inflammatory disease with complex underlying biology. We are now amid a rapidly expanding therapeutic landscape of treatment options for individuals with IBD, yet ADS051 is different and represents a unique therapeutic approach of neutrophil modulation," said Jessica Allegretti, MD, MPH., Crohn's and Colitis Center, Associate Professor of Medicine, Harvard Medical School, Gastroenterology, Hepatology and Endoscopy, Internal Medicine, Brigham and Women's Hospital. "Participants in the multiple ascending dose (MAD) trial with moderately to severely active UC were repeatedly dosed with ADS051. Highly favorable signals of pharmacologic activity and clinical benefit were seen over a relatively short 28-day period. These Phase 1b MAD data indicate that ADS051 may represent an important therapeutic advancement as a safe and effective, once-daily oral therapy for patients with UC." ADS051 is a novel, oral, gut-restricted, small molecule consisting of an active moiety or warhead, covalently linked to a 2,000 molecular weight polyethylene glycol (PEG). ADS051 inhibits two neutrophil-related receptors, multidrug resistant protein 2 (MRP2) which activates hepoxilin A3 (HXA3) neutrophil recruitment or transmigration and formyl peptide receptor 1 (FPR1), a known GPCR found on the surface of neutrophils, important for activation and signaling recruitment. Due to the design of ADS051, it largely remains in the colonic lumen, avoiding wide-spread systemic exposure and subsequent T-cell activation or general immunosuppression. Unlike currently available therapies, ADS051 is intended to positively affect neutrophil-mediated tissue damage, a hallmark of IBD pathology. The ADS051 data generated from these two studies has been submitted to the United States (U.S.) Food and Drug Administration (FDA) within an end-of-Phase 1 meeting. Adiso is currently planning a Phase 2 trial for the treatment of moderately to severely active UC in adults. Publication Links: Small-Molecule Neutrophil Modulator ADS051 is Safe and Well-Tolerated in a Phase 1 Single Ascending Dose Study (Open Press), Safety, Pharmacokinetics, and Clinical Efficacy of ADS051, a Neutrophil Modulator, in Ulcerative Colitis: Results of a Randomized Phase 1b Trial (Open Press) About ADS051 ADS051 is a novel, oral, gut-restricted, small molecule that blocks multidrug resistant protein 2 (MRP2)/hepoxilin A3 (HXA3) and formyl peptide receptor 1 (FPR1) mediated neutrophil epithelial transmigration and activation in human cell-based systems. Its lack of both systemic exposure and blockage of T cell activation is intended to limit general immunosuppression. Unlike currently available therapies, it addresses neutrophil-mediated tissue damage, a hallmark of UC pathology. In a Phase 1b MAD study in patients with moderate to severe ulcerative colitis, ADS051 demonstrated favorable safety and tolerability administered orally, once daily, in patients with moderate-to-severe UC. PK data demonstrated that ADS051 is gut-restricted, as designed, with minimal systemic drug exposure. ADS051 efficacy measures indicate encouraging signals of pharmacologic activity and clinical benefit versus placebo after 28 days of treatment. The Phase 1b MAD data indicate that ADS051 may be an important therapeutic advancement as a safe and effective, once-daily oral therapy for patients with UC. Adiso is currently pursuing additional investigation of ADS051 in a larger Phase 2 clinical study. About Adiso Adiso is a clinical-stage biopharmaceutical company dedicated to improving the health of patients suffering from debilitating inflammatory diseases. This dedication is epitomized by our lead clinical candidates, ADS051, an oral gut-restricted modulator of neutrophil trafficking and activation via inhibition of MRP2 and FPR1 for the treatment of inflammatory bowel disease; and ADS032, a dual NLRP1/NLRP3 inflammasome inhibitor initially being developed for inflammatory diseases of the lung. Adiso has built these development programs upon a rich history of institutional and academic collaboration, including the University of Massachusetts Chan Medical School, the Hudson Institute of Medical Sciences Centre for Innate Immunity and Infectious Diseases in Australia, the University of Edinburgh Centre for Inflammation Research and the University College Cork, Ireland, the APC Microbiome Institute. For more information, please visit or our LinkedIn page Refer to: Scott Megaffin; pr@ (media) View original content to download multimedia: SOURCE Adiso Therapeutics
