Alpha-1 antitrypsin (AAT) has more than two decades of history as a treatment for what is considered a rare-disease population – augmentation therapy for Alpha-1 Antitrypsin Deficiency. In recent years, however, researchers have raised the possibility of AAT as a potential treatment for a startling variety of diseases and conditions, many of them common: COPD/bronchiectasis, type 1 diabetes, cystic fibrosis, Crohn's disease, connective tissue diseases, cardiovascular disease, organ transplant rejection, and viral infections including HIV.
While AAT is a powerful serine protease inhibitor, the recent research has demonstrated that it also has anti-inflammatory, immune-modulatory, and tissue-protective actions. Human plasma is currently the only source of AAT for clinical use, making the supply inherently limited. Should AAT become a treatment option for even one common condition – diabetes or cardiovascular disease for dramatic examples – severe strains on supply could develop. Understandably, many patients with Alpha-1 Antitrypsin Deficiency have expressed concern that widespread use of AAT in treating other conditions might create shortages for its current use as an augmentation therapy. A potential solution for such shortages would be the development of recombinant and/or transgenic AAT, and research is continuing in this area.
To address these developments and concerns, the Alpha-1 Foundation convened the workshop on New Formulations and Applications of Alpha-1 Antitrypsin reported in this issue of the Journal.
This was the Foundation's 12th Gordon L. Snider Critical Issues Workshop, continuing a series begun in 1998. These workshops are aimed at bringing together subject matter experts from around the globe to evaluate issues of importance to the study of Alpha-1 Antitrypsin Deficiency.
A major goal of our critical issues workshops has always been a cross-fertilization of ideas and findings among the leading scientists in many areas of research. We seek to fill in the gaps of knowledge and evaluate areas of research done by investigators from around the world and from many disciplines that may foster or accelerate the development of therapeutic solutions for the clinical manifestations of Alpha-1.
This particular workshop brought together representatives from the academic research, biotechnology and pharmaceutical communities, as well as governmental representatives from the NIH and FDA. The expert presentations covered investigations of every disease or medical condition we have mentioned. In addition, two areas of critical importance were addressed: potential new formulations and sources of supply for AAT, and the regulatory challenges that must be met in order to win approval of AAT for new clinical uses, or to bring a new AAT product to market.
The commentary in this issue, “Novel Therapeutic Uses of Alpha-1 Antitrypsin: a Window to the Future,” draws a strong conclusion with which we heartily agree: “The information presented at the workshop provided a firm basis for future human trials, some of which are likely to show that AAT can be considered a therapeutic agent in several diseases that are not caused by AAT deficiency.”
While the current use of Alpha-1 augmentation is primarily intended to take advantage of its properties as an anti-elastase, much of the current expanded interest in AAT, for example in treating diabetes, is in its powerful anti-inflammatory properties.
The Foundation's belief and hope is that more practical applications for AAT will lead to more investment in production of AAT and ultimately a far greater supply. We are confident that these shared ideas and findings not only will ultimately help patients with other chronic conditions, but potentially accelerate the availability of aerosolized AAT in recombinant form.