Allogeneic Neo-Islets (NIs), an Immune-Privileged Cellular Therapy for T1DM, Is Safe and Effective in Spontaneously Diabetic Pet Dogs, Reducing Insulin Need by up to 50% over Three Years

The purpose of this INAD pilot study was to assess the safety, feasibility and efficacy of NIs in significantly reducing or eliminating a T1DM dog's need for insulin and/or preventing, halting or reversing DM-related damage to a dog's other organs. NIs (3-D organoids made of Mesenchymal Stromal Cells (MSCs) and cultured, partially dedifferentiated islet cells) have been shown preclinically (NOD mouse model) to eliminate the need for exogenous insulin when introduced i.p. Their MSC component provides immune isolation, allowing their allogeneic use without antirejection agents. Hypothesis: Allogeneically administered NIs would safely, durably, and significantly reduce or eliminate the need for exogenous insulin in spontaneously T1DM dogs, as was found in experimental mice. 6 (4 M, 2 F) spontaneously DM, pet dogs; age 1-12 years were treated under INAD 012-776 and followed 3 years. 2×10e5 NIs/kg bw were introduced under ultrasound guidance to metabolically controlled (blood glucose, triglycerides, thyroid, adrenal functions), sedated animals. Dogs were maintained on insulin as needed, and were followed clinically (CBCs, Chemistry panels, Urinalyses, physical examination, imaging, endocrine function) by the PIs and the dogs’ regular veterinarians. Results: Over 3 years, daily insulin needs, blood and urine glucose and fructosamine fell significantly in 5 of 6 dogs; renal function, body weights, CBCs, chemistries were unchanged. Urinary protein decreased; no hypoglycemic events, and immune response to NIs were observed; no AEs or SAEs were attributed to NIs. Redosing and dosing strategies are being tested to try to eliminate exogenous insulin need. Allogeneic NIs are safe and durably effective, and has significant translational relevance. Even partial effectiveness protects from end-organ damage and preserves renal function. A successful Pre-IND meeting for NI use in humans has been held. Disclosure A.Gooch: Board Member; SymbioCellTech, LLC, Employee; SymbioCellTech, LLC, Stock/Shareholder; SymbioCellTech, LLC. C.Westenfelder: Board Member; SymbioCellTech, LLC., Employee; SymbioCellTech, LLC., Research Support; SymbioCellTech, LLC., Stock/Shareholder; SymbioCellTech, LLC.