MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Type 1 diabetes (T1D) is a major health problem affecting over 1.25 children and adults in the United States alone. It also affects our beloved companion animals, with 1 out of every 100 dogs and cats having this condition.
T1D results from an autoimmune condition, where the patient’s body, by mistake, attacks and destroys cells in the pancreas (β cells) that are responsible for regulating blood glucose levels by producing insulin. While injectable insulin represents the standard of care for these patients, it provides an inferior control system relative to functional β cells, leaving the majority of patients at risk for life-threatening complications. Although transplantation of pancreatic islets, which contain replacement β cells, via portal vein injection into the liver, is an attractive therapeutic alternative for these patients, persistent risks and challenges preclude its more widespread clinical adoption. These include rapid destruction and loss of function of the majority of donor cells upon transplantation and the need for life-long immunosuppression.
This study evaluated a novel packaging strategy for the delivery and maintenance of functional donor islets beneath the skin, resulting in rapid and extended reversal of T1D in diabetic mice.
MedicalResearch.com: What should readers take away from your report?
Response: We are working to develop a novel T1D therapeutic strategy that restores glucose-responsive, insulin-release back to the patient’s body. This strategy involves an injectable collagen solution for easy delivery and protection of islets beneath the skin. Immediately upon injection, the collagen forms a highly stable scaffold that promotes islet survival, function, and engraftment without evoking any foreign-body response.
This published report documents the capacity of this proposed strategy for rapid lowering (within 24 hours) and extended maintenance of normal blood glucose values following delivery of syngeneic (beyond 90 days) and allogeneic (beyond 60 days) islets in diabetic mice. It is noteworthy that these results were obtained in absence of systemic immunosuppression. To the best of our knowledge, this represents the first injectable subcutaneous islet delivery strategy that yields rapid lowering and extended control of blood glucose in absence of an inflammatory response, overcoming significant obstacles posed by present-day transplant strategies
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Additional studies are currently underway to further define the functional longevity of allogeneic and xenogeneic donor islets following injection beneath the skin of diabetic mice. Further development and translation of this novel therapeutic strategy targets studies in naturally-occurring diabetic dogs since such results could foster new product development for companion animals (dogs and cats) while, at the same time, contribute outcomes that better predict human clinical responses. The development of a successful and long-lasting glucose-sensitive, insulin-releasing cell delivery therapy for T1D, would dramatically improve the quality of life, health status, and life expectancy for both human and veterinary patients.
Disclosures: The collagen formulation represents a patented technology.
Citation: Clarissa Hernandez Stephens, Kara S. Orr, Anthony J. Acton, Sarah A. Tersey, Raghavendra G. Mirmira, Robert V. Considine, Sherry L. Voytik-Harbin. In-situ type I oligomeric collagen macroencapsulation promotes islet longevity and function in vitro and in vivo. American Journal of Physiology-Endocrinology and Metabolism, 2018; DOI: 10.1152/ajpendo.00073.2018
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