Over 34 million Americans are living with diabetes. An estimated 6.5 million Americans are living with Alzheimer’s disease (AD) and type 2 diabetes mellites (T2DM). Amyloidosis due to aggregation of amyloid-β is key pathogenic event in AD, whereas aggregation of mature islet amyloid polypeptide (IAPP37) in human islet leads to β-cell dysfunction. A hallmark feature of T2DM is the accumulation of islet amyloid polypeptide fibrils in pancreatic islets. Such accumulations form amyloid plaques and cause apoptosis of -cells of islets.
Researchers at NIA used a bioinformatic and molecular biological approaches to identify two novel islet amyloid polypeptide isoforms: IAPPβ, encoding an elongated propeptide of the conventional IAPP and a non-aggregating IAPPγ, which is processed to an unrelated mature IAPP25 instead of IAPP37. They developed a quantitative selective reaction monitoring (SRM) proteomic assay that determined the isoform peptide levels in human clinical plasma and CSF from individuals with early AD were significantly reduced. Further, mature IAPP25 derived from IAPPγ isoform inhibited fibrillation of IAPP37 and amyloid-β efficiently in vitro.
The novel IAPPβ and IAPPγ isoforms could potentially be developed as peptidyl therapeutics to counteract with amyloid forming IAPP37 and amyloid-β in treatments of diabetes and Alzheimer’s disease. These isoforms could also serve as blood-based biomarkers for Alzheimer’s disease. The NIA seeks co-development partners and/or licensees for the further development of these therapeutics and biomarkers.
- Peptide based anti-amyloid medicine
- Potential market applications for neurodegenerative diseases
- Therapy for amyloid diseases, including type 2 diabetes mellitus, Alzheimer’s disease and Parkinson’s disease
- Potential to be developed as peptidyl therapeutics
- Clinical diagnostic blood-derived biomarkers for AD