SBIR Phase I: Islet Targeted Restorative Therapy for Type 1 Diabetes

The broader impact and commercial potential of this Small Business Innovation Research (SBIR) Phase I project lie in demonstrating the efficacy and safety of beta-cell restorative therapeutics in preclinical studies. This will foster investment and partnerships for further clinical development and eventual commercialization. The technology addresses a significant unmet need in the treatment of stage 3 type-1 diabetes (T1D) and other forms of diabetes with severe beta-cell loss. If successful, the innovation could lead to new therapeutic options for millions of patients worldwide, improving their quality of life and reducing healthcare costs associated with diabetes-related complications. Additionally, the successful commercialization of this therapy has the potential to create high-quality jobs within the biopharmaceutical industry, driving economic growth and innovation. This phase 1 project aims to develop antibody therapeutics for the treatment of stage 3 (or clinically overt) type-1 diabetes (T1D) by harnessing the synergistic effects of autoimmune protection via a beta-cell masking antibody, insulin supplementation, and targeted delivery of mitogenic drugs to the pancreatic islet, the specific disease site of T1D. This research initiative will draw upon technical expertise in islet biology and autoimmunity, beta-cell regeneration, antibody-drug conjugation, islet-targeted drug delivery, and therapeutic evaluation in mouse models of T1D. The molecular target of this technology is ZnT8, an islet-specific autoantigen implicated in T1D pathogenesis. Insights into ZnT8 biochemistry, cell biology, and its role in T1D autoimmunity have been translated to address the critical need for beta-cell autoimmune protection and targeted delivery of beta-cell regenerative therapies for patients with stage 3 T1D, with potential applications extending to other forms of severe beta-cell loss, including latent autoimmune diabetes in adults (LADA) and insulin-dependent type 2 diabetes. The outcomes of this proposed research include the development of a novel therapeutic product that could revolutionize the treatment landscape for stage 3 T1D and future expansion to other forms of severe beta-cell loss. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.