New Treatment for hATTR Amyloidosis

Dr. Michael Polydefkis discusses hereditary ATTR amyloidosis and the recently FDA-approved Alnylam’s ONPATTRO™, which is the first and only treatment approved for the polyneuropathy of hATTR amyloidosis.  

Dr. Michael Polydefkis is a neurologist and Director of the Cutaneous Nerve Lab and Associate Professor of Neurology at The Johns Hopkins University School of Medicine in Baltimore, Maryland. He focuses on neuromuscular diseases, particularly peripheral nerve diseases. He served as one of the lead investigators of the APOLLO trial for Alnylam’s ONPATTRO(TM) (patisiran) for the treatment of hereditary ATTR (hATTR) amyloidosis.


Neal Howard: Welcome to Health Professional Radio. I’m your host Neal Howard, thank you for joining us on the program today. Our guest is Dr. Michael Polydefkis, he’s Director of Cutaneous Nerve Lab and Associate Professor of Neurology at Johns Hopkins and he’s joining us on the program today to talk about hATTR. And I will let Dr. Polydefkis give us a little bit of background about himself and tell us all about hereditary ATTR. Welcome to the program Doctor.

Dr. Michael Polydefkis: Thank you very much. I am an neurologist at Johns Hopkins, I am a professor of Neurology and I focus on … nerve disease and over the past 30 years or so I have become increasingly involved in this … rare disease ATTR. It affects fifty to sixty thousand people worldwide but it’s probably an underestimate, there are probably missing cases.

Neal: So what is hATTR or hereditary amyloidosis?

Dr. Polydefkis: Yes, it stands for hereditary transthyretin-related amyloidosis and that’s a mouthful but this is a genetic disease, it’s also more dominant so it means that you have a 50/50 chance of inheriting the trait if one of your parents has it. And if you have the trait, you’re at risk but it’s not a guarantee that you’ll develop the disease. The disease is caused by this mutated protein and the protein with time tends to misfold and when it misfold it clumps and the clumps accumulate in the heart, the nerves in your arms and legs and also in the GI system. And it typically starts in the 50s and 60s, it’s a little bit later in life. But once it starts, it has a steady or upwards progression. You typically see changes in patients between visits every six months. And when this protein clumps and deposits, if it deposits in the heart, people can develop heart failure or causing myopathy so those symptoms will include shortness of breath, difficulty if they walk or go upstairs, they pick up short of breath … If it deposits in the nerves, in the arms and legs, people experience numbness, tingling in the feet and hands and with time, it’s weakness and that ultimately can cause difficulty walking and contribute to people being in a wheelchair, they have difficulty buttoning buttons, turning keys in doors and they require a manual dexterity. In the GI tract, this can cause this paradox of alternating constipation and diarrhea. So the systemic disease, it can take quite a toll on patients and their family.

Neal: Now you mentioned that it is hereditary and that you can get it from either parent. Does it affect males more than females or vice versa or is it 50/50 across the board since there is a 50/50 chance of you contracting the disease?

Dr Polydefkis: Yes … but men tend to do little bit worse in women but both genders are affected.

Neal: So are these symptoms across the board wherever this disease happens to manifest?

Dr Polydefkis: It’s a good question. The symptoms in the early stages can be quite variable so sometimes people experience pain in the feet, burning pain that’s often mistook for a form of myopathy that’s much more common, diabetic myopathy. Other people can have just the  numbness, other people can adopt weakness very early so you could have a period for presentation but the end result is usually similar in that patients develop weakness, numbness in the hands and feet.

Neal: Well let’s talk about Alnylam’s approved, FDA approval of ONPATTRO. What is ONPATTRO and how does it work to combat these symptoms?

Dr Polydefkis: So ONPATTRO is a game changer on many levels. This is a drug that is the first in its class. It’s an … inhibitor so it targets the molecule that can slice the protein and in this instance, it targets the disease-causing mutant protein in hATTR.  So the drug in effect is a laser-guided missile weapon to target the protein’s production mostly in the liver. So the liver makes the best majority of this protein so ONPATTRO targets the liver and reduces the liver’s production of this protein by about 85% on average. So if you’re making less of the mutant protein … less misfolding and less … accumulation and that translates into less disability.

Neal: Does ONPATTRO have the potential to affect any healthy portions of the cell or in the sales production as it eradicates the unwanted proteins?

Dr Polydefkis: Yes, that’s why this protein’s strength is targeting not all proteins it visit but specifically targeting the exact protein that causes the disease so it is very specific in that respect and therefore it contributes to it being very well tolerated.

Neal: Well where can our listeners go and learn some more about ONPATTRO online?

Dr Polydefkis: Certainly Alnylam’s website at has a lot of information about ONPATTRO and also … amyloidosis patients, they can get information about this drug and the result.

Neal: Well I thank you for joining us on the program today Dr. Michael Polydefkis and giving us all this insight into the recently FDA-approved Onpattro thank you for joining us.

Dr Polydefkis: Sure, thank you.

Neal: You’ve been listening to Health Professional Radio, I’m your host Neal Howard. Transcripts and audio of this program are available at and You can also subscribe to this podcast on iTunes, listen in and download at SoundCloud and be sure to visit our Affiliate Page at and

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