Mesentech = Mesenchymal + Technology
Mesenchymal stem cells constantly renew tissues such as hair, skin, nails, bone. They are builder cells.
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.
Mesenchymal stem cell, SEM
Bones are constantly being remodelled, resorbed by osteoclasts and regenerated by osteoblasts.
SEM sheet of new bone forming
©David Gregory & Debbie Marshall
In patients with bone diseases, the balance between bone resorption and bone regeneration is lost.
Normal bone architecture
SEM of subchondral bone, full thickness
While existing treatments can slow down bone degeneration there is currently no safe way to reverse bone loss.
Osteoporotic bone architecture
SEM osteoporotic bone
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 MES-1007 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.
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.
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.
Application
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.
