Science
Osteoblast(Wright Giemsa stain, 100x)
Many bone disease are largely the result of an imbalance between the number of bone-making cells (osteoblasts) and bone removing cells (osteoclasts). In healthy bone, these two types of cells are in balance. To treat a bone disease, we need to restore this balance. There are a number of drugs that block bone resorption but no safe drugs that can restore lost bone. Our technology is based on pioneering research into the mechanisms underlying bone formation.
Bones are Alive
Bones are constantly being remodeled, resorbed by osteoclasts and regenerated by osteoblasts. In patients with bone diseases, the balance between bone resorption and bone regeneration is lost. While existing treatments can slow down bone degeneration there is currently no safe way to reverse bone loss.
Comparison of normal and osteoporotic bone architecture
Turning Stem Cells into Bone-making cells
Bone is in a constant state of remodeling, being turned over, resorbed, and regenerated. these processes are mediated by cells that dissolve bone, osteoclasts, and cells that make bone, osteoblasts. Both of these have a common parent or progenitor cell called mesenchymal stem cells which can be found in the bone marrow.
Stem cells, respond to chemical signals that stimulate and guide their maturation into different cell types. Our drug contains EP4a, a potent chemical signal that guides mesenchymal stem cells to mature into osteoblasts. EP4a was originally developed at Merck and has a very well characterized profile. However and despite the fact that effective drugs like this exist, pharmacological barriers and side effects make treating bone diseases difficult.
Bones are Tough to Drug
In systemic administration where the drug circulates in blood, other organs and tissues absorb the drug as well. What ends up actually reaching the bone, is often a small percentage of the administered dose. Therefore the drug needs to be administered in high doses which can lead to side effects and toxicity. As a result, patients cannot complete their therapy and the treatment fails.
Mesentech’s drug-conjugate C3 avoids systemic exposure and side effects by specifically delivering the drug to bone tissues so as to avoid systemic exposure. This concept, known as a prodrug, makes C3 exceptionally well tolerated.
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C3
