What is bone remodeling?
Bone remodeling (or bone metabolism) is a lifelong process where mature bone tissue is removed from the skeleton (a process called bone resorption) and new bone tissue is formed (a process called ossification or new bone formation). These processes also control the reshaping or replacement of bone following injuries like fractures but also micro-damage, which occurs during normal activity. Remodeling responds also to functional demands of the mechanical loading and inactivity or lack of loading (like with immobilized patients or in zero gravity in space) can lead to extensive bone loss.
An imbalance in the regulation of bone remodeling can result from an imbalance in two sub-processes, bone resorption and bone formation, and can result in many metabolic bone diseases, such as osteoporosis.
Turning stem cells into bone-making cells
Bone is in a constant state of remodelling, being turned over, resorbed (by osteoclasts), and regenerated (by osteoblasts). 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. Mesenchymal stem cells are builder cells, constantly renewing tissues such as hair, skin, nails, bone.
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.
In patients with bone diseases, the balance between bone resorption and bone regeneration is lost.
Bone health is important
The body’s skeleton renews itself every 10 years. Bones are constantly growing, part of multiple systems in the body, and essential for health. 50% of post-menopausal women have bone loss. Astronauts experience rapid bone-loss after only 2 weeks in space.
While existing treatments can slow down bone degeneration there is currently no safe way to reverse bone loss.
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 MES1022 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 it exceptionally well tolerated.
The problem and stages of drug delivery
The focus for the research at Mesentech is to work on the problem of how to safely get therapeutical drugs to where they are needed in the body.
There are many problems to be solved in drug delivery in order that the drug arrives at the correct destination without being damaged, lost, or pre-absorbed somewhere else in the body. Currently in drug therapies a very small percentage of the drugs arrive at the destination successfully. Most drugs are not efficient, like sending a letter to a friend, but having to send 1000 letters and only 1 actually arriving (0.1% efficiency). This means higher doses, and undesirable side effects.
Delivery is an essential problem when developing drug therapies. This one of the primary focuses of the work at Mesentech, to develop a drug delivery system with widespread application for medicine.
The first successful application was the work of Bob Young, who is developing a targeted version of a drug to stimulate bone growth for bone related diseases, either genetic or due to the aging process. The delivery system however can be adapted to other applications, like cancer research.
Thorough the understanding of biological processes and pharmacology the goal is to enable healthier aging via improved drugs and more efficient delivery methods.
This research is stepping stones for the cure of major bone diseases such as osteoporosis.
Learn more about our leading candidate MES1022.