Science

Amyloid Diseases:  The Need for Early Detection and Treatment

Proteins are an essential part of all living organisms. They are composed of amino acids connected into chains called peptides or longer chains called proteins, which fold into 3D structures to perform their normal biological functions. However, sometimes they unfold, misfold, and aggregate into harmful deposits believed to be linked to neurodegenerative and systemic disorders called amyloid diseases. Amyloid diseases affect over 1 billion people worldwide, and there is an urgent need for early detection and treatment of these diseases.

Illustrated for AD

Toxic Soluble Oligomers:  Early Molecular Triggers of Amyloid Diseases

Toxic soluble oligomers are small clumps of misfolded proteins that abnormally form in the brain and other organs.  There are over 50 amyloid diseases, including Alzheimer’s disease and Parkinson’s disease that are associated with different, misfolded toxic soluble oligomer proteins.  These oligomers begin to cause damage to the brain an estimated 10 to 20 years before clinically evident disease. 

Illustrated for AD

The Amyloid Hypothesis

Many experimental Alzheimer’s disease treatments have been based on the “amyloid hypothesis”.  However, therapies that target downstream events such as extracellular amyloid plaques, fibrils and protofibrils, have shown no or limited benefit because the intervention takes place long after the damage has occurred. 

The Amyloid Hypothesis Recast: Targeting A Needle in a Haystack

The Daggett Research Group at the University of Washington approached amyloid diseases in a novel way. By developing and employing innovative computer simulation techniques, they discovered a new protein structure, called alpha-sheet, linked to toxic soluble oligomers. The discovery of this structure and its association with toxicity became the basis for AltPep’s proprietary technology.

AltPep’s platform is designed to specifically target alpha-sheet toxic oligomers: early molecular triggers of disease.  This highly selective approach is analogous to finding a “needle in the haystack”, as illustrated for the many structural and aggregated versions of the Amyloid-beta (Aβ) peptide.

Anti-amyloid monoclonal antibodies currently approved or under investigation for Alzheimer’s disease largely focus downstream of the damage begun by the Aβ peptide toxic oligomers.

AltPep’s Platform: SOBA Diagnostics and SOBIN Therapeutics

AltPep’s de novo designed synthetic peptides are in development to capture toxic oligomers (SOBA diagnostics) and neutralize toxic oligomers and their downstream consequences (SOBIN therapeutics).

AltPep’s growing library is an arsenal that endeavors to specifically target early triggers of amyloid diseases at the molecular level. This collection also serves as the basis for the company pipeline programs.