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 this video from our Vertex Forward animated series, Taking on Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency, or AATD, is an inherited disease that can cause damage to the lungs and the liver. The underlying cause? A genetic mutation that leads to misfolded AAT protein. Misfolded AAT can polymerize (stick together), which prevents it from getting out of the liver. The trapped proteins are toxic to the cells in the liver, causing liver damage. And unfortunately, the small amount of misfolded AAT that manages to leave the liver and enter the bloodstream is mostly nonfunctional and unable to protect the lungs, the primary function of normal AAT protein. Without this protection, the lungs can get inflamed, resulting in chronic bronchitis and emphysema. 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 illustration
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 efficiently protect the lungs

So what's our idea? We want to figure out a way to help the misfolded protein function more like normal AAT. 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 as the lead executive for our program. 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 AATD team has been working together every step of the way. And I want to thank the hundreds of Vertexians who are focused on delivering a potential treatment to people living with AATD.

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, the thing that is really striking to me is how long people have to wait before being diagnosed. Sometimes it feels like a sense of relief to patients to get a diagnosis, because it comes after months or years of feeling sick. Even though that diagnosis reveals a genetic, potentially life-shortening disease, patients are relieved to have a name for why they feel the way they do. Because of these difficulties with diagnosis it's hard to know the true number of people who are struggling with AATD today. As November also marks World COPD Day (November 17), this month holds another opportunity to encourage those with COPD to investigate if there may be another underlying cause to their disease. Through awareness and education, one of our goals at Vertex is to increase disease awareness, especially around the importance of screening and diagnosis.

In addition to our scientists and clinical development teams working to discover and develop potential 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 ​​​​​​

The most rewarding part of this for me, personally, is to play a small part in a large effort to develop potential new medicines that could make a difference in the lives of people who have AATD.