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Alpha 1 Anti-trypsin Deficiency (A1ATD) Research Project

Alpha 1 antitrypsin deficiency (A1ATD) is a genetic disorder due to a mutation in the SERPINA1 gene that encodes for the A1AT protein.  SERPINA1 is synthesized in the liver but the mutation prevents A1AT secretion.  Decreased A1AT blood levels causes an anti-protease and protease imbalance in the lung that leads to emphysema.  There is no cure for A1ATD-related lung disease.  Current standard of care for A1ATD patients is the same for sporadic cases of COPD.  However, the emphysema of A1ATD is less responsive to the standard of care for COPD.  


Treatment for A1ATD includes weekly augmentation therapy by intravascular administration of A1AT to counter the anti-protease imbalance.  However, there are several limits of A1AT systemic augmentation therapy.  First, patients are subjected to the burden of weekly intravascular therapy.  Second, intravenous administration of A1AT has poor drug delivery to the alveoli which is the site of damage.  Third, the therapy is lifelong and the annual cost of A1AT for the medication alone is approximately $80,000-$100,000, which does not even include the ancillary healthcare costs required to administer the product on a weekly basis.  Presently A1ATD is manufactured from the plasma collected by normal volunteers.  There are some disadvantages of plasma-derived manufacturing. First, the cost of logistics and manufacturing is extremely expensive. Second, there is the risk of transmission of blood-borne infections and lot-to-lot variability in potency from donors.

The Institute, in collaboration with the biotechnology industry, is conducting research to develop more effective treatments for A1ATD to the lung.  The Institute is developing gene therapies for this condition.  Also, the Institute is developing new cost-effective approaches to produced A1AT that do not require the use of plasma. 

To advance this research the Institute is developing a diverse biorepository of A1ATD-stem cell models for performing drug development.  The ultimate objective of this application is to apply stem cell technologies to develop lung cells to test our therapy before introduction into patients.  The Institute has developed stem cell technology to create patient-specific induced pluripotent stem (iPS) cells.  The Institute has developed a first-in-class virus-free and oncogene-free iPSC technology from a small blood sample from A1ATD patients.  The ability to create patient-specific iPSC from a small sample of blood allows the ability to create iPSC cells from anywhere in the country.

The research study involves the recruitment of A1ATD patients of diverse age and diverse level of A1ATD-mutations.  Patients should sign up on our patient registry.  Patients selected to participate in the research will be asked to provide medical records to confirm their diagnosis and type of A1ATD mutation. Also, a blood sample will be collected and shipped to the Institute for further processing.

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