Inhibitors of Amyloid Fibril Formation for the Treatment of Type II Diabetes

Invention Novel inhibitors directed against a newly identified sequence, aimed to prevent amyloid plaque formation and beta cell death are currently being developed. These inhibitors present a novel approach to the treatment of Type II Diabetes and prevention of disease progression. They are based on a novel domain in islet amyloid polypeptide (IAPP), the shortest sequence that best mediates the molecular recognition process that leads to the formation of amyloid fibrils.
The Need Type II diabetes is the most common chronic disease in the western world. Current medications for diabetes type II aim to achieve exogenous control of blood glucose levels. Clinical, genetic and biochemical evidence, however, clearly indicate that the aggregation of the amyloid polypeptide (IAPP) into amyloid fibrils (that form plaques) is a major factor in the pathogenesis of the disease, due to the destruction of pancreatic beta-cells by the plaques. Moreover, familial mutations have been identified in IAPP that are linked to early onset of the disease. Preventing the formation of these protein aggregates or inducing their elimination may, therefore, yield an innovative treatment for the disease. Currently, there are no agents on the market to prevent the formation of amyloid plaques. Such an agent would represent a desperately needed new approach in the treatment of this disease.
Potential Applications
· Stand-alone or combination therapy for the treatment of Type II Diabetes

· Prophylactic treatment of individuals with high risk for Type II Diabetes

· Novel therapeutic approach for the treatment of additional diseases involving amyloidosis, such as Alzheimer’s disease.

· In vivo imaging

· Cell or gene therapy
Advantages
· Complimentary to existing therapies.

· Small molecules

· Potential to create superior peptidomimetics.
Stage Proof of concept was achieved with three prototype inhibitory peptides, as well as low molecular weight, non-toxic, aromatic compounds, that were shown to inhibit fibril formation in vitro, as well as improve cell viability.
Reference
· Mazor Y, Gilead S, Benhar I, Gazit E. (2002) Identification and characterization of a novel molecular-recognition and self-assembly domain within the islet amyloid polypeptide. J Mol Biol. 3221013-1024.

· Gazit E. (2002) Mechanistic studies of the process of amyloid fibrils formation by the use of peptide fragments and analogues: implications for the design of fibrillization inhibitors. Curr Med Chem. 9: 1725-1735.
Patent Pending
Tech Transfer Officer Dr. Tamar Raz Office: +972-3-6406580 Fax: +972-3-6406675 Mail: [email protected]

Inventor(s): Ehud Gazit

Type of Offer: Licensing



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