Genetic Testing Program for hATTR Expanded


One year post-launch, the Ambry Genetics and Akcea Therapeutics hereditary ATTR amyloidosis testing program has been used by more than 700 physicians. The free test screens for up to 81 genes that cause hereditary polyneuropathies and up to 92 genes associated with hereditary cardiomyopathies, including hATTR amyloidosis.

Dr Andrew Darlington

Andrew T. Darlington, DO, cardiologist, Piedmont Healthcare

Andrew T. Darlington, DO

Akcea Therapeutics and Ambry Genetics announced that they have expanded their hATTR Compass partnership program to drive additional awareness and education for patients and physicians.

Thus far, more than 700 doctors across the US and Canada have utilized the no-cost, confidential test, which the companies claim can accelerate or confirm the diagnosis of hATTR amyloidosis and providing additional support and resources to people and health care professionals throughout the process. As every first-degree relative of an impacted patient has a 50% chance of carrying the same genetic mutation, successful and accessible screening is of utmost importance.

To find out more about the program, NeurologyLive® spoke with Andrew T. Darlington, DO, cardiologist, Piedmont Healthcare, who has used the program in his own practice. Darlington detailed the process of undergoing the testing, what advantages it offers clinicians, in which patients it can be useful, and where it can be accessed.

NeurologyLive®: Could you provide some background to the development of this program?

Andrew T. Darlington, DO: Hereditary ATTR amyloidosis is a disease state that has been historically attributed to being very uncommon, and I think that we're getting better as time has moved on in terms of diagnosing this problem. It is an autosomal dominant mutation of the TTR gene that leads to this systemic multi-system involvement—the nervous system, the hard and soft tissues, etc.—and the prognosis has been historically quite poor. Like I mentioned, we've done a pretty poor job at screening patients.

For the actual testing program itself, what is involved and really who should we be screening? I think, first off, the purpose of this compass program is to offer confidential genetic testing and screening and the counseling that goes with it. The people that we're identifying are those that obviously have clinically suspected disease, clinically suspected amyloidosis with polyneuropathy, as well as individuals that have a family history of hereditary ATTR amyloidosis. They may not themselves manifest clinically, but they have a first-degree family member that does and has the diagnosis, so those 2 groups are where we're hoping to identify and utilize the genetic testing itself.

What factors go into the decision to utilize the screening and is there an optimal time to screen individuals?

It starts with a clinical diagnosis—we have to have a clinical suspicion. These patients that may present with polyneuropathy of unclear etiology, is it as a tip-off? Those patients with unexplained cardiomyopathy as well. Heart failure specific symptoms, those are kind of some key tenets coupled with abnormal imaging that we may perform either in the cardiology office, which certainly correlates with testing in the neurologist office as well. But, building that clinical suspicion and really supporting it with the appropriate imaging are the kind of factors that go into who we test outside of what I mentioned when it comes to genetic screening.

We should really restrict it to those 2 groups—the people that we clinically suspect based on the factors that I mentioned and the family members of patients with documented diagnosed hereditary ATTR amyloidosis. Basically, if mom has the clinical diagnosis, ultimately, the children should be screened. First-degree relatives of siblings as well, and that's a big part of what we're doing. It's really identifying the at-risk patients who may not be symptomatic, may not have the actual clinical manifestations, but are at-risk.

There's no identified perfect time to screen, but the key is doing it early. That is where we fall short. A lot of this screening or detection happens later on in the disease course, so we're making the diagnosis when patients are very ill and potentially may not have a treatment that's offered to them. The idea is to recognize the disease early and then do the genetic screening shortly thereafter to diagnose the disease. But it all starts with the clinical suspicion and, as I said, that's where we really fall short—thinking about this disease. If we don't think about it, we're certainly not going to test for it.

What does this testing program involve? What is the process?

It's fairly straightforward, which makes this ideal, particularly for clinicians that may not be in major academic centers that are used to doing this sort of thing. Because this is fairly simplistic, I think it really does open up an opportunity for those patients with doctors and providers that practice in remote locations. The process itself starts with just simply getting your hands on the actual kits—the genetic testing kits—whether they are already provided for in the office, or they can also be ordered online on the website As a healthcare professional, you can go online and order your actual hATTR Compass genetic testing kits.

It starts with getting the kit, and then really collecting the samples as step 2. We can do that 1 of 2 ways, through blood or saliva DNA samples, which makes it pretty simplistic. The blood samples, of course, are done in an office-setting, saliva can actually be done, of course, in the patient's home. Then step 3 is really just submitting it for DNA analysis, which is pretty straightforward as well. The results are then received and typically my experience has been it takes anywhere between 2 to 4 weeks. We've been pretty fortunate that we're getting them closer to 2 weeks.

Once those results are received, it’s making a plan for your patient. That may or may not include consultation with genetic counselors which are available to help patients interpret these test results. That's the other big part of this whole program, the hATTR Compass program, is that not only do they provide the testing, but also the genetic counseling program that goes with it. That is very, very important for explaining this sort of stuff to our patients before they're tested, but also offering the counseling after the testing comes back.

Ultimately, once a test is confirmed positive for those patients that don't display symptoms—you're just screening them because you have an index case in the first-degree family member—you follow them very carefully so that if symptoms do arise, we're able to identify early on and then potentially offer treatment early on as opposed to delayed treatment.

Really those 6 steps: ordering, collecting, submitting, receiving results, making the plan, and then watching out for symptoms that don't exist yet is how this testing program really works. It's pretty simplistic, we have used this in our office a number of times and have been very pleased with the process itself and the results.

What do clinicians need to know about this program and how can they get access to it?

What clinicians need to know is that it's easy to access. In the world that we practice in, we like simplistic. We’re bogged down with a lot of different things and multiple obligations so something that's easy to access is key. I think that's important that doctors also feel that. Genetic testing is expensive and cumbersome—the beauty of this is that it's free. It comes to no cost to the patient as a result of the relationship between Ambry Genetics and Akcea Therapeutics, so that's point number 2: it is free of cost to patients. Then, ultimately, in terms of how clinicians can actually get involved, I think if there's interest there it's always good to once again direct back to the website itself. It really does help guide not only the patients but the healthcare professionals as well. It’s, and that really highlights the hATTR Compass program itself between Ambry and Akcea and allows access to the kits and then really gives a little bit more insight in regards to the program itself, who it’s available to and who it isn't.

This is a diagnosis that I think has not been made well and appropriately over the years and there are multiple reasons as to why we've done a poor job at diagnosing this. Number 1 is that it's perceived to be very rare, and I think we're learning now that it's a little more common than we gave it credit for. I think clinicians have always offered other explanation for the symptoms that we're seeing. Polyneuropathy? Maybe it's due to diabetes or something of the sort. If they have cardiac symptoms? Well, heart failure can be due to hypertension and diabetes, but certainly not amyloid. Knowing that this is a very viable etiology for some of these symptoms is important. The nihilistic approach that for years we've not had any sort of treatment to offer patients, and now we have potentially multiple different treatments to offer the appropriate patients.

As for the workup, there was a lot of confusion about how to work this disease process up, but I think it's become a lot more streamlined. Certainly, to make the diagnosis of hereditary TTR, you need genetic testing and what we spoke about for genetic testing itself is it's pretty streamlined and very simple to do, and once again, even available to doctors that are in rural areas that may not have access to major clinical centers.

I practice in Atlanta, but we certainly have more rural clinics that we go to and we're doing this genetic testing far away from academic centers, and we are able to treat our patients appropriately and in in a time-efficient manner. Over 700 physicians today have used the genetic testing in the US and Canada, so it's really catching on and I just love to see that it's continuing to expand that relationship between Ambry and Akcea as we move into the future.

Transcript edited for clarity.


hATTR Compass™ Genetic Testing Program Continues to Expand and Enable Diagnosis and Treatment of Hereditary ATTR Amyloidosis One Year Following Launch [press release]. Boston, MA, and Aliso Viejo, CA: Akcea Therapeutics and Ambry Genetics; Published July 16, 2019. Accessed July 30, 2019

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