Teachable moment in classrooms:

  1. cellular basis of life chapter – concept of one gene, one protein
  2. cellular basis of life chapter – concept of gene mutation leading to protein malfunction
  3. skeletal system chapter – mechanisms of intramebraneous and endochondral ossifications
  4. skeletal system chapter – differentiation of mesenchymal cells into osteoblasts during bone formation.

The news item:  Recently the following report appeared online:

US FDA approves French drugmaker Ipsen’s rare bone disorder drug

(Reuters) -The U.S. Food and Drug Administration (FDA) on Wednesday approved French drugmaker Ipsen’s drug for a rare bone disorder, making it the first treatment available to patients with the condition that causes abnormal bone growth.

The article states that the drug that was approved by the FDA treats a rare, genetic bone disorder called fibrodysplasia ossificans progressiva. The article also states that there are about 800 people worldwide with this disease, which is characterized by abnormal bone formation.

So, Why Do I Care??  While there are relatively few people directly affected by this disorder, the family members also suffer the emotional trauma of seeing a child or young adult becoming immobilized by this disease, as there is no reversal of the formation of unwanted bone. In addition, research into finding pharmaceuticals that regulate bone formation may enlighten us to find treatment for other disorders of bone growth.

Plain English, Please!!! First, let’s talk about how bone forms under normal circumstances. Bone formation is started by local hormone-like proteins, the bone morphogenetic proteins (BMPs) instructing fibroblast-like cells, the mesenchymal cells, to change into chondrocyte (cells of the cartilage) and then into osteoblast. The instruction of BMPs is transmitted to the cell through a receptor (named ACVR1) on the fibroblast and chondrocyte cell surface. Picture a garage door-opener button on the wall of a house. The finger the pushes that button is the BMP protein, and the button is the ACVR1. When finger contacts the button, changes will happen in the house: the electric motor is turned on, and a chain pulls the garage door upward. When the BMP protein contacts the ACVR1, several chemical changes will happen in the cell, and the cell restructures itself into a chondrocyte, and then into an osteoblast, the cell that makes the mineralized bone material.

Second, let’s talk about how fibrodysplasia ossificans progressiva comes about. In this disorder abnormal, unwanted cartilage and bone masses form around joints and inside skeletal muscle. While we all need bones to form our skeletal system, but unwanted bone deforms, and fuses joints and creates pain inside muscles. The genetic mutation of ACVR1, the cause of this disorder, creates a constantly active ACVR1 in fibroblasts within a skeletal muscle or at the edge of a joint. It is like the garage door opener button would get stuck and keep opening and closing the garage door. Thus, those fibroblasts are instructed to restructure into bone forming cells. Therefore, new, unwanted bone form in locations where bone would not normally be present.

Third, let’s talk about how Sohonos moderates bone formation in fibrodysplasia. The active ingredient in Sohonos acts on retinoid receptors located in the nucleus of the fibroblasts. The retinoid receptor then activates a new set of changes that interfere with the ACVR1 action. Imagine that while the garage door is constantly moving, someone (Sohonos) goes into the house through the front door and sends a person from the house to the garage to unplug the motor for the garage door opener. Therefore, no matter how active the signal is coming from the garage door opener button, the action is stopped. Once we slow the ACVR1-stimulated chemical changes inside the fibroblasts, fewer of those cells will turn into bone forming cells, lesser amount of bone will be formed, and the symptoms of the disorder will moderate.