The science Faze is advancing is going to reshape the way we treat disease.
Recent discoveries in cell biology have uncovered a fundamentally new understanding of how cells work. In addition to the traditional membrane-bound organelles, scientists have discovered a growing class of “membraneless” organelles, called biomolecular condensates, which play key roles in the healthy functioning of cells.
Biomolecular condensates are dynamic clusters which can contain proteins and nucleic acids within a cell. They form by liquid-liquid phase separation, a process similar to oil separating in water.
These droplet-like clusters coalesce and disperse within cells, serving as an organizational strategy to dynamically segregate certain molecules from the wider environment of the cell. This allows cells to rapidly respond to changing conditions, such as stress and perform certain actions, such as DNA repair, signaling and intracellular transport.
This revolutionary insight is key for healthy cell function and has important implications in disease.
Groundbreaking research by Faze’s co-founder J. Paul Taylor has demonstrated that condensates are at the root of many related neurological diseases.
Disease-causing mutations in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and inclusion body myositis (IBM) are associated with dysfunction in the assembly and behavior of a type of condensate called the stress granule. Stress granules form in the cell cytoplasm.
Mutations within certain proteins in a stress granule can promote greater viscosity, or “stickiness,” of the condensate. This shift alters the capacity of the condensate to disassemble and creates an environment that encourages protein aggregation within the cell.
In the case of ALS, this can promote the formation of fibrillar aggregates of TDP-43 that are hallmarks of the disease.
Faze is targeting key proteins to rebalance the dynamics of stress granules…
…thus preventing the hardening of disease-causing fibrils within.
Myotonic dystrophy is linked to another condensate, referred to as aberrant nuclear RNA foci.
In myotonic dystrophy, the overexpression of repeat RNAs leads to the accumulation of RNA foci in the cell nucleus. These RNA foci, in turn, bind up important cellular proteins, preventing them from carrying out their normal cellular functions and leading to disease pathology.
Faze is working to identify the key components and regulators of these aberrant nuclear foci. Targeting these proteins therapeutically will dissolve the nuclear foci, thus liberating sequestered proteins and restoring normal cellular function.