Developing Drugs for Diseases of Protein Aggregation by Structure-Guided Technologies
ADRx's ADvantage Platform leverages over twenty years of pioneering academic research into the structure of ordered protein aggregates. This research has shown at the atomic-level that fibrillar ordered aggregates make up the molecular architecture of amyloid fibrils and biomolecular condensates that play a role in a variety of diseases.
Amyloid fibrils form when the body's normal proteins unravel and expose adhesive regions that cause the proteins to stick together producing repeating rope-like structures. Over 20 different proteins are known to form amyloid fibrils in the body in over 50 diseases such as Alzheimer's, ALS, cardiomyopathy, and diabetes. Our ADvanatage Platform positions us to develop therapies against these diseases.
In the case of biomolecular condensation the process of unraveling and forming higher order fibrillar structures are a part of the native function of proteins in forming biological structures such as stress granules. Aberrant biomolecular condensation has been implicated in a variety of neurodegenerative, cancer, and infectious diseases.
Therapeutics to intervene in this process will therefore need to be specific and selective to the aggregated forms of the target protein to be successful in improving health without undue side-effects.
Recent advances in structural biology (microcrystalline X-ray diffraction, ssNMR, cryoEM and nanocrystal electron diffraction) have lead to a better understanding of the assembly of amyloid and biomolecular condensates at an atomic-level and has enabled new ways of using structure-based drug design against these structures.
Structure-based drug design against these types of targets has traditionally been hampered by the lack of conventional binding pockets on ordered fibrils. ADRx uses its proprietary technology to identify segments along the ordered aggregates that drive their assembly, define the molecular binding sites along these segments, and use them to discover small molecules that module their aggregation.
ADRx ADvantage Platform™
ADRx was founded to develop and commercialize novel therapies that prevent the abnormal aggregation of proteins that cause disease. The ADvantage Platform™ begins with a detailed structural picture of each target protein or protein segment and uses a combination of computational and empirical screening tools to discover small molecules that can modulate its aggregation with a degree of selectivity and specificity superior to other screening approaches.