Alpha-1-Antitrypsin Deficiency: Disease Management and Learning from Studies

Greulich, Timm

doi:10.1080/15412555.2017.1286166

Cited by 9 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We applied the procedure developed for BSA@ZIF‐8 to synthesize biocomposites of α 1 ‐antitrypsin, AAT. AAT is a member of the serine protease inhibitor (serpin) superfamily and is currently under investigation as a biotherapeutic for the treatment of several neutrophilic diseases, for the control of inflammatory, immunological, and tissue‐protective responses . Three different samples were synthesized using the flow setup, employing the residence times used for the preparation of BSA@ZIF‐8 biocomposites (Supporting Information, Section S7).…”

Section: Figurementioning

confidence: 99%

Continuous‐Flow Synthesis of ZIF‐8 Biocomposites with Tunable Particle Size

et al. 2020

View full text Add to dashboard Cite

Zeolitic imidazolate framework (ZIF) biocomposites show the capacity to protect and deliver biotherapeutics. To date, the progress in this research area is based on laboratory batch methods. Now, the first continuous flow synthetic method is presented for the encapsulation of a model protein (bovine serum albumin, BSA) and a clinical therapeutic (α1‐antitrypsin, AAT) in ZIF‐8. The in situ kinetics of nucleation, growth, and crystallization of BSA@ZIF‐8 were studied by small‐angle X‐ray scattering. By controlling the injection time of ethanol, the particle growth could be quenched by ethanol‐induced crystallization from amorphous particles to ZIF‐8 crystals. The particle size of the biocomposite was tuned in the 40–100 nm range by varying residence time prior to introduction of ethanol. As a proof‐of‐concept, this procedure was used for the encapsulation of AAT in ZIF‐8. Upon release of the biotherapeutic from the composite, the trypsin inhibitor function of AAT was preserved.

show abstract

Section: Figurementioning

confidence: 99%

Continuous‐Flow Synthesis of ZIF‐8 Biocomposites with Tunable Particle Size

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The wild type allele coding for the normal protein is noted as M (M1-M6; serum level ≥0.9 mg/mL), whereas most of the AAT variants are in S and Z forms comprising three major genotypes: ZZ, SZ and SS that are associated with reduced serum levels compared to wild-type. The homozygous (ZZ) genotype in the European population is estimated at approximately 0.01-0.02% [53,54] A study carried out with 224 cohorts across 65 countries estimated that 253,404 individuals possess the ZZ genotype worldwide. The Z mutation is located at the base of the RCL loop and affects the loop structure and causes severe AAT deficiency [55].…”

Section: Alpha-1 Antitrypsin Deficiencymentioning

confidence: 99%

“…It is recommended that every patient with COPD be screened for AATD to facilitate the early diagnosis of AATD, distinguish them from other COPD patients, and provide suitable treatment early on. Intravenous AATD augmentation therapy is the currently accepted treatment method, and it has shown promise in attenuating the loss of lung function [53].…”

Section: Alpha-1 Antitrypsin Deficiencymentioning

confidence: 99%

“…AAT drugs might constitute a potential treatment for COVID-19 and this can be a potential target of antiviral intervention. AAT augmentation therapy has been used for decades to treat emphysema in AATD patients [53]. Intravenous infusion of AAT has been monthly administered for 12 months at the rate of 250 mg/kg increased serum AAT concentration by 5-fold in lung epithelial lining fluid without causing side effects [110].…”

Section: Aat Protection Against Covid-19mentioning

confidence: 99%

See 1 more Smart Citation

COVID-19 Pathology Sheds New Light on Balance between Neutrophil Proteases and Their Inhibitors

Radic¹,

Silva²

2022

Preprint

View full text Add to dashboard Cite

Excessive neutrophil influx and activation in lungs during infections, such as manifest during the ongoing SARS CoV-2 pandemic, have brought neutrophil extracellular traps (NETs) and the con-comitant release of granule contents that damage surrounding tissues into sharp focus. Neutro-phil proteases, which are known to participate in NET release, also enable the binding of the viral spike protein to cellular receptors and assist in the spread of infection. Blood and tissue fluids normally also contain liver-derived protease inhibitors that balance the activity of proteases. In-terestingly, neutrophils themselves also express the protease inhibitor alpha-1-antitrypsin (AAT), the product of the SERPINA-1 gene, and store it in neutrophil cytoplasmic granules. The absence of AAT or mutations in the SERPINA-1 gene promote lung remodeling and fibrosis in diseases such as chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and increase the risk of allergic responses. Recent observations point to the fact that re-duced activity of AAT presents a major susceptibility factor for severe COVID-19. Here, we focus attention on the mechanism of neutrophil elastase (NE) in NET release and its inhibition by AAT as an additional factor that may determine the severity of COVID-19

show abstract

“…In the best-case scenario, an improvement in FEV 1 within the range of less than 100 mL can also be obtained with other drugs such as ICS, which are less expensive and more convenient than inhaled AAT [24]. A possible lack of (or small) effect of AAT on FEV 1 should not mislead us from recognising the crucial effect of augmentation therapy in reducing the rate of destruction of lung parenchyma in emphysema associated with AATD [25][26][27].…”

mentioning

confidence: 99%