Targeting the metabolic pathways that underlie disease
Metabolism governs how every cell in the body senses energy, generates fuel, and responds to stress. When key metabolic pathways, AMPK and mTOR, are dysregulated cells lose the ability to sense and use energy efficiently, driving obesity, metabolic disease, and chronic inflammation.
Cambrian is developing therapeutics designed to restore these critical metabolic sensing functions.
The two critical metabolic sensing functions
Two interconnected signaling networks sit at the center of this decline: AMPK and mTOR. Together they govern whether a cell burns fuel or stores it, grows or maintains itself. When this balance breaks, the consequences manifest as some of the most prevalent cardiometabolic diseases in the world.
The AMPK network
AMPK is the master regulator of cellular energy balance. When energy demand rises, AMPK activates its signaling network, mobilizing energy reserves from the fat and liver, and burning that energy in the mitochondria of the muscle and other organs.
AMPK activity declines as we age, impairing the cell's ability to adapt to shifts in energy demand. This loss of metabolic flexibility contributes to insulin resistance, fat accumulation, and the development of many metabolic diseases.
Therapeutic Goal
Restore AMPK Network activation to re-engage the cell's energy-sensing capacity and increase metabolic rate.
mTOR regulation
mTOR is a central regulator of cellular growth and nutrient sensing, functioning through two distinct complexes: mTORC1, which promotes anabolic, pro-growth processes, and mTORC2, which supports metabolic homeostasis and immune function.
mTORC1 becomes chronically over-activated as we age, driving sustained pro-growth signaling while suppressing essential cellular maintenance processes. This imbalance between growth and repair contributes to the accumulation of cellular damage and the development of many age-related diseases.
Therapeutic Goal
Selectively inhibit mTORC1 while preserving mTORC2 activity, restoring the balance of growth and repair characteristics of healthy cells.
