During the 1970s, a large number of different genetic patterns were identified for Alpha-1. These are called alleles of the AAT gene. First 10, then 50, and now over 100 different alleles for AAT have been discovered. About 34 of these alleles are associated with a deficiency of AAT. The rest are slight variations from the normal AAT gene that seem to cause no problems.
In the 1980s, investigators started to test whether it would be possible to replace or augment the deficient AAT protein in individuals with Alpha-1. This work was carried out primarily at the National Institutes of Health (NIH) facilities in Bethesda, Md. Investigators there isolated and purified AAT from normal volunteers, then administered it intravenously to patients with Alpha-1. They identified a dose that, when administered every week, could maintain AAT blood and lung levels at or above the level thought to protect against lung injury. This therapy became Prolastin®.
Cutter Laboratories was the company that owned the product being tested at the NIH. Working with the NIH, they showed the product was safe and could augment the levels of AAT in the blood and lungs. The next step in drug development would be to do a study to prove the drug protected against the progression of emphysema. Experts in the field were brought together to discuss the design of such a study. They concluded, however, that such a study would take many years to complete, and it would be virtually impossible to study the number of Alpha-1 patients needed, since so few had been identified at that time. It was expected that Prolastin would never be approved without such a study.
However, because there was no other available treatment for Alpha-1, and Prolastin could safely increase the amount of AAT levels in the lungs, the U.S. Food and Drug Administration (FDA) decided to approve Prolastin for prescription in the United States. Several countries in Europe also approved the drug. Prolastin became readily available in the United States in the beginning of 1988. Over the next several years, the companies marketing Prolastin changed from Cutter to Cutter/Miles, and then from Miles to Bayer. As of early 2003, two additional intravenous drugs have been approved for the treatment of Alpha-1: Aralast, marketed by Baxter Healthcare, and Zemaira, made by Aventis-Behring/ZLB Behring. Prolastin is now marketed by Talecris Biotherapeutics. Other medications may be approved in the future.