Vertex Forward: Taking on Alpha-1 Antitrypsin Deficiency

Nov 12, 2020

Vertex Forward: Taking on Alpha-1 Antitrypsin Deficiency

Every year in November,Vertex joins the alpha-1 antitrypsin deficiency community in recognizing AATD Awareness Month. To help raise awareness about this important and underdiagnosed disease, we’re pleased to share the next video in our Vertex Forwardanimated series,Taking on AATD.

Alpha-1 antitrypsin deficiency, or AATD, is an inherited disease that can cause damage to the lungs and the liver. A genetic mutation leads to misfolded AAT proteins getting trapped in the liver. This prevents the proteins from traveling to the lungs, which is where they help protect the lungs. Without this protection, the lungs can get inflamed, resulting in chronic bronchitis and emphysema. The trapped AAT also causes damage to the liver. There is currently no cure for AATD, and those living with the disorder have a reduced life expectancy due to the progressive nature of the disease.


AAT Protein
Left: Healthy liver and lungs where the AAT protein is produced in the liver and delivered to the lung and organs

Right: Misfolded AAT protein builds up in the liver where it is produced, damaging the liver and making it unable to travel efficiently to the lungs 


At Vertex, we’re trying to address the underlying cause of AATD by building on our expertise and 20 years of experience in cystic fibrosis(CF), another genetic disorder caused by a misfolded protein. It’s an example of how we’re living our values — serial innovation, commitment to patients, pursuit of excellence and collaboration — and applying them to a different disease.  

Having worked on our CF program for many years, I’m excited to turn my attention to AATD. We wouldn’t be where we are today without the dedication of our scientists and a cross-functional team that is working tirelessly for patients who are waiting. From evolving our understanding of the biology of a disease to developing molecules, our team has been working together every step of the way.  

One of the biggest challenges with AATD is that many people don’t know they have it. The way the disease presents varies, and genetic testing isn’t always part of a workup for a patient. Lung symptoms typically present in adults ages 40 to 50, and they are often misdiagnosed as having asthma or smoking-related chronic obstructive pulmonary disease (COPD). In adults with lung manifestations, a diagnosis of AATD is typically delayed by five to seven years after the onset of symptoms due to lack of awareness of AATD and misdiagnosis. Liver problems can present at any time, as early as childhood, or not at all. It’s our hope that by helping to increase awareness of this disorder, the various ways AATD can present can be caught earlier, because an accurate and early diagnosis can impact how the disease is managed. 

When listening to patients, I’m often surprised to hear that they feel a sense of relief when they get a diagnosis, which usually comes after months or years of feeling sick. Even though that diagnosis reveals a genetic, potentially life-shortening disease, they are relieved to have a name for why they feel the way they do. Because of these difficulties with diagnosis it is difficult to know the true number of people who are struggling with AATD today. Through awareness and education, one of our goals is to ensure increased screening and diagnosis.   

 In addition to our scientists and clinical development teams discovering and developing new medicines, we have teams at Vertex dedicated to diving deep into the available data to improve our understanding of the epidemiology and natural history of this disease and the needs of the AATD community. At the same time, it’s also important that criteria for getting tested for AATD have been clearly established. Recommendations about testing were published in the journal Chronic Obstructive Pulmonary Diseases in 2016. 

Who should be tested for AATD? 

1. All people with COPD, regardless of age or ethnicity

2. Anyone with unexplained chronic liver disease

3. People with necrotizing panniculitis, granulomatosis with polyangiitis or unexplained bronchiectasis 

4. Family members (siblings, parents, children, extended family) of people who have been tested and carry an abnormality in the gene that causes AATD should be provided genetic counseling and offered testing ​​​​​​

Throughout my career, I’ve always strived to work in areas where I believe there is a need for innovation. This proved to be true for cystic fibrosis, and we’re working on AATD with that same innovative spirit and sense of determination. 


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