a1-antitrypsin therapy for non-deficient individuals: integrating and mitigating cross-pathology inflammatory and immune responses to the injured cell
Abstract
Human a1-antitrypsin (AAT) is an endogenous circulating anti-inflammatory glycoprotein presently infused to patients with genetic AAT deficiency. It represents a regimen of remarkable safety for life-long weekly slow drip intravenous infusion sessions. Based on its anti-inflammatory properties, it has been suggested that it may be of benefit in medical conditions outside genetic AAT deficiency. In the past five years, reports on the testing of AAT therapy for various unmet medical needs had surfaced, and a novel clinical parameter appears to have become critically relevant: AAT insufficiency. The molecule is programmed to rise during inflammatory flares, as well as during the 3rd trimester of pregnancy and with age; yet in some instances, one meets conditions in which it might fail to rise. The review focuses on advances in the utilization of AAT therapy outside AAT deficiency in the past years, depicting well-coordinated preclinical and clinical studies, leaps in basic research in as far as the mechanism of AAT is concerned and novel binding partners of AAT, including lipids. The collective data places endogenous and exogenous AAT as centering on the critical junction between the immune system, inflammation and the injured cell. Thus, clinical trials span conditions as sparse as type 1 autoimmune diabetes, acute myocardial infarction, lung transplantation and cystic fibrosis. The phenomenon of immune cell repopulation appears to bridge several pathologies and expose a window of opportunities for tissue preconditioning using AAT therapy, whether in the case of bone marrow transplantation or cell/organ grafting. The safety of AAT is by now demonstrated to embrace broader patient populations both in as far as age and underlying clinical condition. Together with the growing interest in drug repurposing, and the capacity to formulate novel AAT-based agents, we may expect further extension of this primordial molecule for the bettering of our health.
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DOI: http://dx.doi.org/10.18103/imr.v3i5.451
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