{"id":8715,"date":"2023-07-12T18:24:16","date_gmt":"2023-07-12T16:24:16","guid":{"rendered":"https:\/\/centroandaluzalfa1.org\/?p=8715"},"modified":"2023-07-12T18:24:18","modified_gmt":"2023-07-12T16:24:18","slug":"aatd-news","status":"publish","type":"post","link":"https:\/\/centroandaluzalfa1.org\/en\/aatd-news\/","title":{"rendered":"AATD NEWS"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\"><strong>AATD NEWS<\/strong><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>What is happening in the AATD investigation?<\/strong><\/h3>\n\n\n\n<p><strong><strong>The DAAT web portal contains DAAT news and we summarize the following points of interest<\/strong><\/strong><\/p>\n\n\n\n<p>Alpha-1 antitrypsin deficiency (AATD) is a rare entity that is associated with the development of chronic obstructive pulmonary disease (COPD) and pulmonary emphysema in adults and liver disease and panniculitis in children and adults.<\/p>\n\n\n\n<p>Research into rare diseases requires the development of patient registries that include a large number of cases to find out their characteristics and natural history. Without research, there is no cure.<\/p>\n\n\n\n<p><\/p>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-28f84493 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-image size-large is-style-default\"><img fetchpriority=\"high\" decoding=\"async\" width=\"1024\" height=\"1024\" src=\"https:\/\/centroandaluzalfa1.org\/wp-content\/uploads\/2023\/07\/Novedades-DAAT-1024x1024.jpg\" alt=\"\" class=\"wp-image-8708\" srcset=\"https:\/\/centroandaluzalfa1.org\/wp-content\/uploads\/2023\/07\/Novedades-DAAT-1024x1024.jpg 1024w, https:\/\/centroandaluzalfa1.org\/wp-content\/uploads\/2023\/07\/Novedades-DAAT-300x300.jpg 300w, https:\/\/centroandaluzalfa1.org\/wp-content\/uploads\/2023\/07\/Novedades-DAAT-150x150.jpg 150w, https:\/\/centroandaluzalfa1.org\/wp-content\/uploads\/2023\/07\/Novedades-DAAT-768x768.jpg 768w, https:\/\/centroandaluzalfa1.org\/wp-content\/uploads\/2023\/07\/Novedades-DAAT.jpg 1080w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p>The <a href=\"https:\/\/www.earco.org\/\" target=\"_blank\" rel=\"noreferrer noopener\">EARCO<\/a> registry is an initiative of the EARCO Clinical Research Collaboration (CRC) of the European Respiratory Society (ERS). This is an international, observational and multicenter study whose main objectives are:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Generate high-quality clinical data from AATD patients in a longitudinal and long-term manner.<\/li>\n\n\n\n<li>Understand the nature and prognosis of individuals with AATD.<\/li>\n\n\n\n<li>Investigate the effect of AAT replacement therapy and other therapies on the progression of the disease.<\/li>\n\n\n\n<li>Expand knowledge about the course of the disease in patients with severe AATD with genotypes other than Pi*ZZ.<\/li>\n<\/ul>\n<\/div>\n<\/div>\n\n\n\n<h3 class=\"wp-block-heading\">News of the knowledge of AATD mutational variants<\/h3>\n\n\n\n<p><strong>Alpha 1 antitrypsin deficiency is a mutation-sensitive disease<\/strong><\/p>\n\n\n\n<p>This is because AAT is a protein that has conformational flexibility with several regions involved in a large structural rearrangement necessary for its protease inhibitory function.<\/p>\n\n\n\n<p>This protein is susceptible to mutations that cause misfolding, inactivation, or intracellular accumulation of polymers that cause liver damage.<\/p>\n\n\n\n<p><strong>Rare variants may be more frequent than expected and therefore, in discordant cases, standardized detection of the S and Z alleles needs to be complemented by gene sequencing and structural approaches.<\/strong><\/p>\n\n\n\n<p>Structural characterization of novel pathogenic SERPINA1 mutations encoding circulating AAT could provide new insights into the mechanisms of AAT misfolding in liver and lung diseases.<\/p>\n\n\n\n<p><strong>This could have important implications for molecular diagnostics and therapeutic development.<\/strong><\/p>\n\n\n\n<p>The authors discuss the utility of computational modeling in providing supporting evidence for the pathogenicity of rare single nucleotide variations.<\/p>\n\n\n\n<p><strong>Five variants, four of them previously unknown, of the SERPINA1 gene are characterized, defining new alleles that contribute to AATD.<\/strong><\/p>\n\n\n\n<p>Author of the commentary: Dr. Carlota Rodr\u00edguez Garc\u00eda. Pneumology Service. University Hospital Complex of Santiago de Compostela, Galicia.<\/p>\n\n\n\n<p>Resource:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36527073\/\" target=\"_blank\" rel=\"noreferrer noopener\"> PubMed National Library of Medicine<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\">News of AATD Treatments<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Treatments for AATD patients<\/h3>\n\n\n\n<p>Patients with chronic obstructive pulmonary disease (COPD) and severe alpha-1 antitrypsin (AATD) deficiency who meet criteria for this may benefit from intravenous (iv) AAT replacement therapy with weekly infusions of purified human AAT. .<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">Inhaled route<\/h4>\n\n\n\n<p>A non-invasive treatment strategy is the administration of human AAT by the inhaled route, either by nebulization or dry powder inhalers (DPIs). Both methods have advantages and disadvantages.<\/p>\n\n\n\n<p>In the case of liquid aerosols, penetration of the particles into the respiratory tract, a key requirement for therapeutic effect, may be a potential problem.<\/p>\n\n\n\n<p>Additionally, during nebulization, proteins can be denatured and inactivated by oxidation or aggregation at the air-liquid interface or by mechanical stress and thermal degradation.<\/p>\n\n\n\n<p>On the other hand, the production of DPIs is frequently carried out by processes, such as freeze-drying or spray-drying, which can expose the protein to thermal and physical-chemical stress, causing a reduction in its activity.<\/p>\n\n\n\n<p>However, the use of dry powder inhalers is more accepted, with greater adherence to treatment by patients.<\/p>\n\n\n\n<p>On the other hand, it improves the quality of life with respect to the use of nebulizers, since the time needed for administration is drastically reduced compared to nebulization.<\/p>\n\n\n\n<p>The authors of this article investigate an alternative treatment strategy of recombinant AAT (rAAT) replacement of Escherichia coli in dry powder produced by spray drying, delivered by inhalation via DPI.<\/p>\n\n\n\n<p>Resource: <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36496391\/\" target=\"_blank\" rel=\"noreferrer noopener\">PubMED<\/a> <\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Results of the research<\/h3>\n\n\n\n<p>Since the spray-drying process can be a source of stress leading to protein degradation or denaturation.<\/p>\n\n\n\n<p>Researchers have paid special attention to the effect of formulation parameters on protein stability, as well as possible mechanisms. of degradation.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">In this way, purified, active and endotoxin-free rAAT was produced.<\/h4>\n\n\n\n<p>In the formula using L-leucine and mannitol as excipients after identifying the compromise conditions for protein activity and good aerodynamic performance.<\/p>\n\n\n\n<p>Parenteral infusion replacement therapy aims to achieve a serum concentration of at least 11 \u00b5M, which is estimated to correspond to a pulmonary epithelial fluid concentration of 1.7 M (8.8 mg\/dL).<\/p>\n\n\n\n<p>To achieve this concentration, about 50 mg of powder should be administered (2 capsules of 25 mg of the formulation).<\/p>\n\n\n\n<p>These authors present a novel and innovative research paper on replacement therapy with rAAT of Escherichia coli administered by inhalation via DPI.<\/p>\n\n\n\n<p><strong>This work could represent an alternative to current AATD treatments, avoiding its weekly parenteral administration, generally in day hospitals.<\/strong><\/p>\n\n\n\n<p>Author of the comment: Dr. Francisco Casas Maldonado. Pneumology Service. San Cecilio Clinical University Hospital of Granada.<\/p>\n\n\n\n<p>Resource:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36527073\/\" target=\"_blank\" rel=\"noreferrer noopener\"> PubMed National Library of<\/a><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36559248\/\" target=\"_blank\" rel=\"noreferrer noopener\"> Medicine<\/a><\/p>\n\n\n\n<div class=\"wp-block-buttons is-layout-flex wp-block-buttons-is-layout-flex\">\n<div class=\"wp-block-button\"><a class=\"wp-block-button__link wp-element-button\" href=\"https:\/\/centroandaluzalfa1.org\/en\/news-on-alpha-1-antitrypsine-deficiency\/\">Read more news<\/a><\/div>\n\n\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>What is happening in the DAAT investigation? We discover the news of the DAAT in terms of mutational variants<\/p>\n","protected":false},"author":5,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"disabled","ast-hfb-above-header-display":"disabled","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"disabled","ast-breadcrumbs-content":"disabled","ast-featured-img":"disabled","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[1,8,70],"tags":[],"class_list":["post-8715","post","type-post","status-publish","format-standard","hentry","category-daat-al-dia","category-eventos-y-congresos-daat","category-pacientes-daat"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>AATD NEWS - Centro Andaluz Alfa-1<\/title>\n<meta name=\"description\" content=\"AATD News! 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