Autophagic processes affect many aging, neurodegenerative, inflammatory, metabolic, and infectious diseases at the cellular level, acting in a primary or secondary capacity. The ability to direct an autophagy-modifying drug toward a specific disease outcome is therefore highly desirable.
Biophagy’s business model focuses on the discovery of unique, high content methods to identify pharmaceutical modulators of autophagy, including their development for clinical and diagnostic applications in diseases of high unmet need. The company is currently utilizing proprietary screening platforms based on the autophagy biomarker, LC3, to discover and develop both known pharmaceuticals and new chemical entities (NCEs).
LC3, the soluble light chain (17kDa) of microtubule-associated protein 1A/1B, is a widely used marker of autophagic activity in mammalian systems. It is therefore an excellent target for measuring the relative effects of autophagy stimulants or inhibitors and can be quantified in human cells using Biophagy’s proprietary technology. During the generation of autophagosomes, cytosolic LC3-I is converted to a phosphatidylethanolamine derivative, LC3-II, which becomes associated with autophagy-related membranes. The generation of LC3-II by proven autophagy modulators can subsequently be demonstrated as a confirmatory measure of autophagic stimulation or inhibition (Fig. 1).
Fig. 1. The effect of autophagy-inducing drugs on LC3 expression and autophagosome development in a human cervical epithelial cell line.
Fluorescence Spectra of Autophagy Stimulants in Human Cells
Hyperspectral confocal imaging: intracellular fluorescence spectra (Sandia NL)
In addition to therapeutics, Biophagy will also develop autophagy-directed diagnostic protocols to determine the level of a patient’s autophagic efficiency, thus acting as a “companion diagnostic” to identify which patients will benefit most from autophagic modulation.
Targeted diseases are represented by (but not limited to) the following therapeutic areas:
- Diseases of aging (e.g., Alzheimer’s Disease)
- Neurodegenerative disorders (e.g., Huntington’s Disease, Parkinson’s Disease)
- Autoimmune disorders (e.g., MS, lupus, RA)
- Pulmonary diseases (e.g., COPD)
- Inflammatory disorders (e.g., Crohn’s Disease)
- Infectious diseases (e.g., tuberculosis, HIV/AIDS, hepatitis B and C)
- Cancer (e.g., pancreatic)
- Metabolic diseases (e.g., types I/II diabetes, metabolic syndrome, obesity)
Biophagy is currently identifying potential therapeutic/diagnostic agents for use in diseases with high unmet medical need and is in the process of discovery testing and lead selection.