Alpha-1 antitrypsin: Associated diseases and therapeutic uses

Kandregula, Chaya A. Babu; Aseervatham, G. Smilin Bell; Bentley, Gary T.; Kandasamy, Ruckmani

doi:10.1016/j.cca.2016.05.028

Cited by 8 publications

(9 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human α1‐antitrypsin is a 52 kDa glycoprotein with three N ‐glycans and its primary biological function is the inhibition of neutrophil elastase and proteinase 3 . Currently, only human plasma‐derived α1AT ( pl α1AT) is available as treatment of α1AT‐deficiency in humans .…”

Section: Introductionmentioning

confidence: 99%

Case study on human α1‐antitrypsin: Recombinant protein titers obtained by commercial ELISA kits are inaccurate

Hansen

Kildegaard

Lee

et al. 2016

Biotechnology Journal

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Case study on human α1‐antitrypsin: Recombinant protein titers obtained by commercial ELISA kits are inaccurate

Hansen

Kildegaard

Lee

et al. 2016

Biotechnology Journal

View full text Add to dashboard Cite

“…Numerous studies have suggested and provided both experimental and clinical evidence that AAT could be therapeutically useful in a wider spectrum of inflammatory and immune-related diseases [24–29]. These diseases include other inflammatory lung diseases such as COPD-emphysema not related to severe AAT deficiency [30, 31], cystic fibrosis [32–34], autoimmune diseases such as type I diabetes [35], and transplantation rejection [36]. Thus, there is a growing interest for alternative AAT preparations due to the protein’s apparent beneficial effect in clinical conditions other than inherited AAT deficiency-related emphysema [36].…”

Section: Introductionmentioning

confidence: 99%

“…These diseases include other inflammatory lung diseases such as COPD-emphysema not related to severe AAT deficiency [30, 31], cystic fibrosis [32–34], autoimmune diseases such as type I diabetes [35], and transplantation rejection [36]. Thus, there is a growing interest for alternative AAT preparations due to the protein’s apparent beneficial effect in clinical conditions other than inherited AAT deficiency-related emphysema [36]. Although numerous small molecule anti-elastase preparations [30], a wide spectrum of AAT products modified for enhanced efficacies [26, 37, 38], and many expression systems producing a wide spectrum of recombinant AAT exist [39–42], none have reached the U.S. marketplace to date.…”

Section: Introductionmentioning

confidence: 99%

An oxidation-resistant, recombinant alpha-1 antitrypsin produced in Nicotiana benthamiana

Silberstein

Karuppanan

Aung

et al. 2018

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Proteases and reactive oxygen species (ROS) have long been implicated in playing key roles in host tissue injury at sites of inflammation dominated by macrophage activations and/or neutrophil infiltrations. Imbalances between proteases/antiproteases and ROS/antioxidants are recognized to contribute to amplification of inflammatory-based host tissue injury. This has been especially well-documented in such respiratory tract diseases as chronic obstructive pulmonary disease, cystic fibrosis, and acute respiratory distress syndrome. Inflammation-related protease/ROS disequilibria are further confounded by recognition that proteases can increase ROS by several different mechanisms and that ROS can inactivate proteases. The major human antiprotease, alpha-1 antitrypsin (AAT), is dramatically inactivated by ROS. AAT deficiency is the most prevalent genetic predisposing factor leading to emphysema, a condition treated by replacement infusions of plasma-derived AAT (hAAT) at a cost of up to $200,000 per year per patient. An updated method for production of a plant-made recombinant AAT (prAAT) engineered for enhanced oxidation resistance compared to hAAT is presented. Plant-made recombinant AAT shows comparable antiprotease activity to hAAT, and retains full activity under oxidative conditions that would deactivate hAAT. Additionally, we show that prAAT has similar effectiveness in preventing neutrophil elastase-induced cell death in an in vitro human bronchial epithelial cell culture model. We conclude that prAAT is potentially a "biobetter" AAT product that could be made available to individuals with a wide spectrum of inflammatory disorders characterized by overly aggressive neutrophilic infiltrations.

show abstract

“…In some cases it is reported that the RCL, even in an uncleaved state, can insert into the beta sheet of an adjacent serpin molecule forming inactive protein aggregates [31][32][33][34][35][36]. These aggregates then can accumulate in the endoplasmic reticulum and cause both serpin deficiency and cellular dysfunction [37][38][39][40][41].…”

mentioning

confidence: 99%

“…Treatment with AAT as either purified protein has proven highly effective and when expressed in viral vectors as gene therapy has great promise. Thus treatment with the AAT serpin protein is already an established clinical therapeutic agent for use in AAT deficiency in emphysema and potentially in other disease states, such as cirrhosis [38][39][40][41].…”

mentioning

confidence: 99%