Augmentation therapy is a medical treatment designed to supplement or replace a substance that is missing or deficient in the body. This therapeutic approach aims to restore a normal level of the substance to prevent or slow the progression of a related disease. By introducing the missing component from an external source, the therapy helps the body regain a specific protective function. The treatment acts as a long-term maintenance strategy rather than a cure, helping to manage the underlying cause of the condition.
Understanding the Need for Augmentation Therapy
The need for this specific augmentation therapy arises from Alpha-1 Antitrypsin Deficiency (AATD), an inherited disorder. AATD is caused by mutations in the SERPINA1 gene, resulting in a shortage of functional Alpha-1 Antitrypsin (AAT) protein circulating in the blood and lungs. This deficiency leaves these organs vulnerable to damage.
The AAT protein’s primary role is to protect the lungs from neutrophil elastase, a powerful enzyme released by white blood cells during the immune response. AAT acts as an inhibitor, neutralizing the elastase once its job is complete so it does not attack healthy tissue.
When AAT levels are low, the active elastase breaks down delicate protein structures in the lungs, particularly elastin, which maintains the elasticity of the air sacs (alveoli). This uncontrolled breakdown leads to the progressive destruction of lung tissue, manifesting as emphysema, a form of Chronic Obstructive Pulmonary Disease (COPD). Augmentation therapy replenishes this protective shield against continuous lung damage.
The Mechanism of Action
The mechanism of augmentation therapy involves directly replacing the missing AAT protein. The therapeutic product is purified AAT protein, derived from the pooled plasma of thousands of healthy human donors. This exogenous protein is molecularly identical to the functional AAT protein the patient cannot produce adequately.
Once infused into the bloodstream, the administered AAT circulates throughout the body and diffuses into the fluid lining the lungs. The goal is to raise the AAT concentration above a protective threshold, typically 11 micromolar (µM). Achieving this level allows the infused AAT to engage with and neutralize neutrophil elastase.
This process corrects the protease-antiprotease imbalance, restoring the lung’s natural defense capacity. The introduced AAT protein binds to the destructive elastase, preventing it from digesting structural proteins in the alveolar walls and slowing the progression of emphysema.
Administration and Treatment Logistics
Augmentation therapy is delivered through an intravenous (IV) infusion, meaning the medication is administered directly into the patient’s bloodstream. The typical dosing regimen involves a standard dose of 60 milligrams per kilogram of body weight, administered once every week. This frequency is necessary to maintain the AAT protein levels consistently above the protective threshold in the blood and lungs, as the protein has a half-life of about three to five days.
The infusion process requires preparation, including reconstituting the powdered medication or preparing the liquid form, and then carefully monitoring the rate of infusion. The treatment can be administered in several settings, including a hospital outpatient clinic, a dedicated infusion center, or at the patient’s home with the assistance of a trained home-care nurse. For long-term access, an IV catheter is often used, and some patients may opt for an implanted vascular access device, or port, to protect peripheral veins.
Patient Eligibility and Expected Outcomes
Patient eligibility for augmentation therapy is determined by specific criteria to ensure the treatment is targeted to those most likely to benefit. Individuals must have a confirmed diagnosis of severe AATD, typically defined by specific genetic variants like PiZZ or PiNull, which result in very low serum AAT levels. Furthermore, the patient must have objective evidence of lung disease, such as emphysema or airflow limitation confirmed by pulmonary function tests.
The treatment is generally recommended for adults who are non-smokers or ex-smokers, as continued smoking significantly accelerates lung destruction and can render the therapy less effective. Augmentation therapy is not typically recommended for individuals with AATD who have normal lung function or for those whose only manifestation is liver disease. This selectivity ensures that the expensive, long-term therapy is used for its intended purpose of preventing pulmonary deterioration.
Augmentation therapy is a disease-modifying treatment, not a cure for AATD. The treatment cannot reverse any damage already sustained by the lungs or restore lost lung function. The primary and realistic goal is to slow the rate of decline in lung function over time and potentially reduce the frequency or severity of pulmonary exacerbations. Studies suggest that the therapy attenuates lung tissue loss, managing the expectation that it is a lifelong commitment to disease stabilization.