Plerixafor and GLP-1 Analogue Trial Aims to Preserve Insulin Secretion in New-Onset Type 1 Diabetes

Type 1 Diabetes (T1DM) is a severe autoimmune disease characterized by the immune system's destruction of pancreatic beta-cells, leading to absolute insulin deficiency. Current treatments focus on exogenous insulin replacement, but there is no known cure that addresses the underlying autoimmunity or promotes beta-cell regeneration. The progressive loss of beta-cell function necessitates lifelong insulin therapy, which carries risks of hypoglycemia and long-term complications. This proposed trial aims to address this gap by combining immunologic reset with regenerative approaches to restore self-tolerance and promote islet repair.

This abstract describes a proposed interventional trial designed to evaluate an 'immunological reset' approach in subjects with new-onset Type 1 Diabetes. The protocol involves T-cell depletion therapy and anti-inflammatory treatment to restore self-tolerance. Following this, autologous, peripheral-blood mobilized hematopoietic CD34+-enriched stem cells will be administered. Stem cell mobilization will be facilitated by Plerixafor. Concurrently, a long-acting GLP-1 analogue will be used to promote pancreatic islet regeneration and repair. The primary short-term goal is to demonstrate greater preservation of endogenous insulin secretion compared to controls, and to establish the safety of this nonmyeloablative treatment without requiring chronic immune suppression.

This abstract outlines a proposed clinical trial protocol; therefore, no empirical findings are reported from a completed study. The expected outcomes and hypothesized benefits of this 'immunological reset' approach are detailed. The trial aims to demonstrate that subjects with new-onset Type 1 Diabetes undergoing this combined therapy will exhibit significantly greater preservation of endogenous insulin secretion compared to a control group. The intervention is also hypothesized to be safe and well-tolerated, crucially avoiding the need for chronic immune suppression, which is a major drawback of many current autoimmune disease treatments. The combination of T-cell depletion, anti-inflammatory agents, Plerixafor-mobilized CD34+ stem cells, and a long-acting GLP-1 analogue is expected to synergistically restore self-tolerance and promote pancreatic islet regeneration. The ultimate goal is to achieve a functional cure by halting autoimmune destruction and fostering beta-cell repair.

The foremost expected outcome is the demonstration that this nonmyeloablative treatment is safe, without the need for chronic immune suppression, while preserving endogenous insulin secretion.