Basic (Target Identification)
Over 32 million Americans are living with Diabetes and newly diagnosed cases of type 1 and type 2 diabetes is increasing. A defining feature of type 2 diabetes mellitus (T2DM) is the accumulation of islet amyloid polypeptide (IAPP) fibrils in pancreatic islets. Such accumulations form amyloid plaques, referred to as islet amyloidosis. Mounting evidence suggests that islet amyloidosis plays a causative role in the development and progression of ß-cell dysfunction in T2DM. Currently, approved therapies for T2DM modulate the production of or sensitivity to insulin, but do not specifically target islet amyloidosis. Thus, there is an unmet need to develop new diabetes treatments that inhibit islet amyloidosis. Additionally, any therapy preventing IAPP amyloidosis may prevent other potential amyloidogenic peptides from forming amyloid and amyloid plaques.
Insulin C-peptide, co-secreted from secretory granules within pancreatic β-cells alongside mature insulin and IAPP, plays a key role in keeping insulin and IAPP non-aggregated by charge-based interactions. Researchers at the NIA uncovered a novel variant of the C-peptide, named Cα- peptide, having 19 amino acids and lacking -sheet and hairpin motifs present in the middle portion of the conventional 31 amino acid length C-peptide. The newly discovered Cα-peptide derives from a novel proinsulin of 74 amino acids and inhibits IAPP amyloid fibrillation more efficiently than conventional C-peptide. There is an opportunity for Cα-peptide derivatives to be developed as a therapeutic inhibiting islet amyloidosis. Researchers also identified decreased levels of processed Cα-peptide in T2DM pancreatic islets compared with control islets. This finding revealing the possibility for Cα-peptide as a clinical diagnostic marker for islet dysfunction and, potentially, neurodegenerative diseases. This finding reveals the potential for Cα-peptide as a clinical diagnostic marker for islet dysfunction and, potentially, neurodegenerative diseases.
The NIA seeks co-development partners and/or licensees for the further development of Cα-peptide as a therapeutic that inhibits islet amyloidosis.