University of Pittsburgh researchers have identified genes which when silenced can improve glucose tolerance, insulin secretion and insulin sensitivity. Targeting these genes using viral-mediated small interfering RNA (siRNA) may be a novel therapeutic strategy for managing type 2 diabetes (T2D).
Description
Around one in ten people in the United States (US) are living with diabetes and T2D accounts for 90–95% of cases. Rates of T2D are rising, linked to the worsening obesity epidemic, given that obesity can lead to insulin resistance and significant stress on pancreatic -cells involved in regulating insulin secretion. Chronic insulin resistance can lead to -cell dysfunction and loss, resulting in T2D. Transforming growth factor- (TGF-) interacting with smad2 has been implicated in the regulation of these pancreatic -cells. Silencing smad2 genes in mice has led to improved glucose and insulin responses and may be a novel therapeutic target for T2D.
Applications
• Diabetes
• Gene therapy
Advantages
T2D is a growing public health concern and the 7th leading cause of death in the US. Blindness, lower limb amputation and a variety of cardiovascular complications can impact on patient quality of life. Treatment options currently include lifestyle changes, diet and exercise, and medication but these are not always effective or suitable. Novel treatment strategies are needed to tackle this unmet clinical need.
This novel approach may target the underlying cause of T2D through the inhibition of TGF-/smad2 signaling pathways, protecting -cells from the dysfunction caused by insulin resistance, and increasing -cell proliferation potentially inhibiting the development and progression of T2D.
Invention Readiness
Proof of concept in vivo studies in mice have shown acute knock down of smad2 genes specifically in -cells can improve insulin secretion and ameliorate glucose intolerance, and other damage, including hepatic insulin sensitivity caused by a high fat diet (a model for obesity-induced dysglycemia). Overall, loss of smad2 was shown to increase -cell proliferation following induced physiological stress from a high-fat diet and even following 60% partial pancreatectomy. Future work will use an intrapancreatic ductal infusion system to infuse siRNA against smad2 with an adeno-associated virus in non-primates to investigate the potential of siRNA to reverse T2D.
IP Status
https://patents.google.com/patent/WO2022226091A1
