Correcting functional defects in pancreatic cells to treat diabetes

Manuel Irimia.

Universitat Pompeu Fabra (UPF), Spain.

Diabetes is characterised by a progressive loss of function in the pancreatic beta cells responsible for producing and releasing insulin. Current treatments help control blood glucose levels but do not address the mechanisms underlying beta cell dysfunction. This project aims to develop a first-in-class RNA therapy that restores pancreatic beta cell function.

The strategy builds on previous research in which the team identified a highly specialised programme of islet-enriched microexons in beta cells. These tiny RNA segments are selectively incorporated into specific genes that regulate glucose sensing, insulin production and secretion. Modulation of this programme alters beta cell function. The team has developed splice-switching antisense oligonucleotides that modify the inclusion of selected microexons in laboratory cells leading to increasing insulin secretion, and will now test the most promising candidates in preclinical models of diabetes.

Precise modulation of RNA processing could provide longer-lasting benefits than simply forcing insulin production. The strategy represents a novel precision platform with potential applications not only in diabetes but in other disorders driven by beta cell failure.

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