Rare Disease Report

Managing hATTR Amyloidosis

MAY 07, 2018
Mathew Maurer, M.D.


In an interview with Rare Disease Report, Mathew Maurer, MD, Arnold and Arlene Professor of Cardiology at Columbia University, explained the standard of care and current management tactics for individuals with hATTR Amyloidosis.

Maurer: The standard treatment, or I should say management for this condition, is very different than what we hope treatment will be. Currently we manage the condition and the manifestations by treating the symptoms of, if you will, heart failure. We encourage patients to stay physically active, avoid smoking, adhere to a relatively low sodium diet, assuming they have a clinical syndrome a heart failure which means they’re swollen and full of water, and we also encourage self-management skills. For instance, weigh yourself on a daily basis because when you have some dietary indiscretion, eat a little extra salt, you can gain a lot of fluid pretty quickly and that can really exacerbate your baseline symptom—make you have much shorter breath. Those are kind of management strategies—none of them are treating the underlying condition. 

However, we’ve learned a great deal about this particular disease. We’ve learned that this protein transthyretin, which is a small protein with only 127 amino acids. It fits together with 3 identical transthyretin proteins to make a 4-leaf clover, and the disease is mediated by the fact that when the protein falls apart or misfolds, the pieces get stuck in the heart.

So, there are actually 3 emerging treatment strategies. The first for cardiac amyloid is what’s called transthyretin stabilization. These are small oral drugs that fit in-between the leaves of the protein and actually keep the protein together, so called stabilizing it, the theory being that if the protein does not fall apart, you will slow down the progression or ideally halt the progression of the disease. There are several compounds that have been investigate in this area, one called diflunisal, which is a non-steroidal anti-inflammatory agent that’s available by prescription.

Then more recently there’s a drug called tafamidis, which recently reported in a large Phase 3 trial that they met their primary endpoint, which means the drug was reportedly successful, and we’re anxious to learn more. So that’s one of the first standard therapies that will come for transthyretin and cardiac amyloidosis.

The second strategy is what’s called silencing in which drugs usually administered by intravenous or by subcutaneous, underneath the skin injection, can amazingly go to the liver, go to the liver cells, and tell them, “Shh don’t make the protein anymore. Continue to do everything else you do but silence the production of that particular protein.” These aren’t pie-in-the sky ideas, these drugs exist, and they’ve been tested. They’ve mainly been tested in patients who have mutations in the transthyretin gene that causes a neuropathy, problems in the nerves not a cardiomyopathy, but they have been shown in recently conducted Phase 3 trials to be very effective. We have a lot of hope for those agents to be to patients with transthyretin cardiomyopathy. 

The final emerging idea at this point, which is really early in its infancy, is the idea of using what we would call monoclonal antibodies to target the amyloid that already exists inside the heart and try to activate the immune system and allow it, if you will, like pac-man to chew up and eliminate the amyloid that already exists. Those are the 3 strategies currently in development for the treatment of the problem.  

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