Tag: autoimmune disease

Teachable moment in classrooms:

1. muscle tissue chapter – structural components of the neuromuscular junction
2. muscle tissue chapter – role of acetylcholine receptor in muscle excitation
3. immune system chapter – components and function of complement system

The news item:  Recently the following news item appeared online:

FDA approves drug for adults with generalized myasthenia gravis

AstraZeneca has announced FDA approval of Ultomiris, a long-acting C5 complement inhibitor for the treatment of adults with generalized myasthenia gravis. According to a company press release, Ultomiris (ravulizumab-cwvz) was approved for adult patients who are anti-acetylcholine receptor antibody-positive, which represents 80% of people with the disease.

The article states that the disease myasthenia gravis affects about 90,000 people in the US, and that Ultomiris is a long-acting C5 inhibitor that allows early treatment leading to lesser amount of damage.

So, Why Do I Care??  The article’s citation of the number of affected individuals shows that this is not a minor disease. In its advanced stage myasthenia gravis can be deadly, or at least life threatening; the loss of muscle strength prevents the patients from many daily activities, which causes a decreased quality of life.

Plain English, Please!!!  First, let’s talk about what myasthenia gravis is. Myasthenia gravis is an autoimmune disorder where the patient’s own immune system attacks and damages the neuromuscular junction. The target of the immune system is a molecule, the acetylcholine receptor, in the neuromuscular junction. The acetylcholine receptor physically binds to the messenger molecule called acetylcholine released by the neurons. So, destruction of the receptor makes it impossible for skeletal muscles to understand that they are supposed to contract. The damaged muscles no longer contract with normal force, thus the patients develop muscle weakness that affects movement, and can endanger inhalation causing respiratory distress.

Second, let’s talk about how myasthenia gravis causes damage. The first action of the immune system in myasthenia gravis is to make antibodies that stick to the acetylcholine receptors. The second action is that the antibodies in the neuromuscular junction attract the proteins of the complement system. The 9 complement proteins stick to each other, assemble on the cell membrane, and eventually open a hole in the muscle cell membrane. Imagine an excavation crew where all 9 members have to work together to dig a hole. Those holes in the muscle cell membrane cause the most significant damage to the neuromuscular junction.

Third, let’s talk about how Ultomiris works. The active ingredient in Ultomiris covers up a complement protein (#5), and prevents the piling up the rest of the complement proteins. Without the assembly of all of those proteins the excavation crew never starts to dig, the hole never forms in the muscle cell membrane, and the neuromuscular junction can stay relatively undamaged. That kind of protection slows deterioration, and preserve muscle strength in the patients.