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  1. Celiac.com 02/25/2005 - Today a team of scientists at Alba Therapeutics Corporation and the University of Maryland School of Medicine report a direct link between zonulin-mediated increased intestinal permeability and Type 1 Diabetes (T1D) in the BB/wor Rat Model of Diabetes. Even more remarkable, the investigators were able to successfully prevent the onset of the autoimmune destruction of pancreatic beta cells and the onset of T1D in these animals by using the specific zonulin blocker AT-1001. Daily, oral administration of the drug beginning before the onset of auto-immunity in the diabetic prone rats cut the incidence of the disease by 2/3, and completely blocked the development of autoimmune antibodies in the treatment responders. Published in the latest issue of the Proceedings of the National Academy of Science (PNAS), these results constitute the first successful result in preventing the autoimmune process characteristic of T1D by blocking the zonulin-mediated abnormal intestinal permeability. These results go well beyond the development of a prevention strategy for T1D, says Dr. Alessio Fasano, lead author of the paper and Professor of Pediatrics, Medicine and Physiology and The University of Maryland School of Medicine. They open a new field of investigation in which the interplay between host and environment at the mucosal level may help us understanding the molecular basis of many diseases. These results reinforce our conviction that the zonulin pathway provides a roadmap for the discovery and development of innovative products to treat many important diseases, including diabetes, in ways previously thought to be inconceivable stated Dr. Blake M. Paterson. These preclinical proof-of-concept results with AT-1001 support the salvaging of beta cell function in pre-diabetics or in new-onset diabetes, giving us the impetus to rapidly move through the development process, bringing this dream to a reality for treatment in the diabetes community. T1D is an autoimmune disease that results in the destruction of the insulin producing cells of the pancreas, the islet beta cells. Current treatment of T1D is limited to the administration of insulin and other medications to treat the consequence of diabetes, elevated blood sugar and the complications thereof. The inability to treat the cause of T1D - a process known as autoimmunity, in which the bodys immune system attacks the beta cells of the pancreas - has been the key obstacle to the freeing patients from the yoke of this disease. Autoimmune diseases are thought to occur in individuals with the genetic pre-disposition to attack and destroy various organ tissues by the bodys own immune system. This immune misrecognition is thought to be triggered by the presence of an environmental stimulus; in the case of T1D, the trigger is unknown. While the majority of research efforts have focused on identifying the trigger of T1D and modifying immune pathways, little is known about how such a trigger might enter the body and about how such an entry-way might serve as a target for the treatment of the disease. The discovery of zonulin - a gatekeeper of intestinal barrier function, and its involvement in celiac disease, led to the hypothesis that its malfunction could be involved in a series of other autoimmune diseases characterized by a leaky gut, including T1D. Previous work by Dr. Alessio Fasano has shown a close association of celiac disease in children at risk of developing T1D and led to the novel discovery research in support of AT-1001. About Alba: Alba Therapeutics is a Baltimore based biopharmaceutical company dedicated to commercializing disease-modifying therapeutics and drug delivery adjuvants based on the zonulin pathway. Albas lead molecule, AT-1001, is targeted towards the treatment of Celiac Disease and Type 1 Diabetes and is in the final stages of pre-human testing. Contact Alba Therapeutics Corporation, Baltimore Dr. Blake Paterson, 410-522-8708
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