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. heart chapter – layers of the heart wall
  4. heart chapter – conduction system of the heart and arrhythmias

The news item:  Recently the following article appeared online:

NHS England ” First ever life-saving treatment for rare heart condition available on the NHS

NHS patients with a life-threatening heart condition are set to benefit from a cutting-edge new medicine which can significantly reduce the risk of hospitalisation and death. The drug, tafamidis, is the first ever approved treatment for a cohort of patients in England with a rare heart condition known as transthyretin amyloidosis cardiomyopathy (ATTR-CM), where clumps […]

The reporting states that the drug tafamidis treats patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM), and that this disease comes from deposition of clumped proteins in the heart, presents symptoms of shortness of breath, fatigue, fainting, and may result in heart failure and death. In clinical trials tafamidis reduced hospitalizations by 41%.

So, Why Do I Care??  ATTR-CM currently affects about 6 million people un the USA, and 5-7000 new diagnoses happen each year. Heart disease limits daily activity of the patients, and lower their quality of life; therefore, designing treatments is always a positive development.  Because amyloidosis can appear in many organs, tafamidis might show the potential path to the treatment of those disorders.

Plain English, Please!!!  First, let’s talk about what amyloidosis is. In general terms, amyloidosis is an abnormal accumulation of proteins into clumps large enough to be seen through a light microscope. Many times those clumps interfere with the normal functioning of organs. In the case of ATTR-CM the transthyretin gene has mutations that cause the transthyretin protein to be misshaped. The normal transthyretin proteins join together in groups of four, because some amino acids create sticky surfaces that hold the four proteins together. Picture four eggs, each having a drop of glue at the pointed end. When four eggs are touching each other at their pointed ends they are stuck together like the four transthyretin proteins, and because the sticky surfaces are all covered up, no more eggs can be part of this complex.  When the transthyretin protein is misshapen, the positions of the sticky surfaces change on the protein, and thousands of eggs (proteins) would stick to each other randomly, forming large clumps of eggs (proteins), the amyloids.

Second, let’s talk about how amyloidosis damages the heart. The clumps of transthyretin pile up in between the cardiac muscle cells, and with time connective tissue builds up next to the amyloids. The mass of transthyretin and connective tissue resist the force of contraction, so blood is not moved efficiently from the heart chamber. Unequal pumping of blood from the left versus right side of the heart causes congestive heart failure. In addition, amyloid clumps can also disturb the conduction system of the heart, and cause disturbances of the heart’s rhythm, and that again lead to heart malfunction.

Third, let’s talk about how tafamidis works. The molecule tafamidis acts like a Velcro patch between the pointed ends of the eggs, the transthyretin proteins.  This way even many of the misshapen transthyretin proteins can be built into a four -membered transthyretin complex, so less transthyretin is available to form amyloids, thus the harmful effects are reduced.