How A2M Works
Alpha-2-macroglobulin (A2M) is a large protein that circulates in the blood. It's one of the body's broad-spectrum protease inhibitors, meaning it can neutralize many different protease enzymes rather than
just one.
A2M works like a Venus flytrap. Each molecule carries "bait" regions that proteases recognize and cut. Cutting the bait triggers A2M to change shape and close around the enzyme, trapping it so it can no longer break down tissue. The trapped complex is then cleared from the body.
Laboratory studies have shown that A2M can inhibit enzymes involved in cartilage breakdown, including ADAMTS-4 and ADAMTS-5 (Tortorella et al., 2004) and ADAMTS-7 and ADAMTS-12 (Luan et al., 2008).
In joints with osteoarthritis, natural A2M levels are too low to keep up with the enzymes that are active. Our hypothesis is that delivering concentrated A2M directly into the joint can block those enzymes and slow cartilage loss. Our first-generation therapy, APIC™, tested this idea using a patient's own A2M. CYT-108 takes it further with an engineered version.
Independent preclinical research also suggests that A2M may support cartilage-building cells, increasing type II collagen and aggrecan (Guo et al., Cartilage, 2025). This has not yet been shown in people.
Get updates on CYT-108 and the science behind it.
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