ANTI-AMYLOID THERAPEUTIC DEVELOPMENT
BASED UPON AMYLOID AND PROTEOGLYCAN EXPERTISE

 

What Is Amyloid?

 

Amyloid refers to a chemically diverse group of extra-cellular proteins with common morphological properties, staining characteristics and x-ray diffraction spectra. These proteins consist of non-branching, aggregating fibrils that form insoluble toxic deposits in the brain or in different systemic organs.

 

Amyloid can be classified by the specific protein found in these deposits. Thus, beta-amyloid protein accumulates in the brains of all Alzheimer's disease patients and is directly linked to the memory loss associated with this disease. Likewise, alpha-synuclein protein accumulates in the brains of Parkinson's patients and is linked to loss of motor function.

 

Still other amyloid proteins contribute to the morbidity of certain systemic diseases. The over-expression and deposition of IAPP in the pancreas facilitates the destruction of insulin-producing cells (i.e. beta-cells) and accelerates the onset of type 2 diabetes. It is thought that accumulation of IAPP leads to beta-cell death in approximately 90% of patients with type 2 diabetes. In another “amyloid disease,” AA amyloid fibril deposits appear in a variety of organs including heart, kidney, liver, spleen and gastrointestinal tract in patients with underlying chronic inflammatory conditions such as rheumatoid arthritis or inflammatory bowel disease. Systemic AA amyloidosis generally leads to organ failure (i.e. heart or kidney failure) 3-7 years after the onset of the disease. As many as 17 different amyloid proteins have now been identified that may be associated with these issues.

 

What Are Proteoglycans?

 

Proteoglycans (“PG”) are a group of glycoproteins consisting of complex carbohydrate macromolecules called glycosaminoglycans (“GAGs”) attached to a protein backbone.  Normally, they function as structural components of cellular basement membranes or act as receptor-like molecules on the surface of cells.

 

However, in diseased states, proteoglycans contribute to the cause of amyloid diseases by accelerating amyloid formation and growth, and by blocking the degradation and clearance of fibrillar amyloid deposits.

 

ProteoTech is researching the role proteoglycans play in amyloid disease pathogenesis and has identified several proteoglycan variants that may help researchers explain how some of the major diseases are initiated.