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Kamada starts Alpha-1 Antitrypsin phase 2 clinical trial to prevent lung transplant rejection

Kamada has started a phase 2 clinical trial with its proprietary drug Alpha-1 Antitrypsin (AAT) for preventing rejection in lung transplants, as part of a collaboration with Baxalta.
Source: Drug Development Technology - Category: Pharmaceuticals Source Type: news

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The risk of primary graft dysfunction (PGD) of donor lungs and early postoperative mortality after lung transplantation (LTx) increases with prolonged preservation times. PGD is triggered by early infiltrating neutrophils which release large amounts of elastase-related serine proteases and inflict irreversible damage on lung graft after cold ischemic storage. Cold ischemic storage for only 6 hours is generally accepted, when lungs are cooled down and preserved in Perfadex immediately after their removal from donors.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Source Type: research
Primary graft dysfunction (PGD) is the most serious early complication and it occurs within the first 72 hours post-transplantation. There is currently no specific treatment to prevent or treat PGD. Ischemia reperfusion injury (IRI) is an important component of PGD. Alpha 1 antitrypsin (A1AT) is a serine-protease inhibitor that inhibits excessive proteolytic enzymes so they don't accumulate and break down normal tissue. A1AT primarily inhibits neutrophil elastase, an important contributor to IRI.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Source Type: research
Vascular damage and primary graft dysfunction increases with prolonged preservation times of transplanted donor lungs. Hence, storage and conservation of donated lungs in protein-free, dextran-containing electrolyte solutions like Perfadex ® is limited to about six hours.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Source Type: research
Conclusions Induction with sc28AT promotes early cardiac allograft protection in hu5C8-treated NHPs. These results support further investigation of prolonged selective CD28 inhibition with CD40/CD154 blockade in NHP transplants.
Source: Transplantation - Category: Transplant Surgery Tags: Original Basic Science—General Source Type: research
Long-term survival after lung transplantations is still poor, mainly due to chronic lung allograft dysfunction, with its most frequent phenotype being bronchiolitis obliterans syndrome (BOS), characterized by a high neutrophil recruitment.Given the multiple therapeutic benefits of alpha1-antitrypsin (AAT) -including inhibition of neutrophil elastase activity- in the past years few studies were published, suggesting that the interaction between AAT and the human neutrophil elastase (HNE) may play a role in the graft acceptance after lung transplantation.Our aim is to study the concentration of AAT and HNE in Bronchoalveolar...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Transplantation Source Type: research
The objective of the present study was to determine if administration of A1AT during EVLP can improve donor lung quality after prolonged hypothermic preservation.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Source Type: research
Alpha 1-antitrypsin (AAT) deficiency (AATD) is a genetic condition characterised by low serum levels of AAT and is associated with a high risk of developing early-onset pulmonary emphysema, especially in cigarette smokers [1]. The most common deficiency alleles among Caucasians are Pi*Z (Glu342Lys) and Pi*S (Glu264Val), and the majority of individuals with severe AATD are Pi type ZZ. According to available literature, PiZZ AATD comprises about 1–5% of all chronic obstructive pulmonary disease (COPD) cases [2]. Given the importance of the protease/anti-protease imbalance in causing Pi*Z-related emphysema [3], intraven...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: COPD and smoking Original Articles: Research letters Source Type: research
Discussion α-1-Antitrypsin Deficiency (A1AT) is a common single-gene mutation disease that is homozygous recessive. The normal allele is called M and the most common abnormal allele is Z. There are other alleles though. The gene codes for one of the primary protease inhibitors in the serum, thus those who are homozygous for the Z gene are sometimes referred to as “PIZZ” or “PIZ.” α-1-Antitrypsin is found in all body tissues but is especially important in the serum and lung. As noted it is one of the primary neutrophil protease inhibitors in the serum, and acts to neutralize these enzymes...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Alpha-1 antitrypsin (AAT) deficiency is a common inherited metabolic disorder caused by a point mutation in the SERPIN1A gene. A small portion of homozygous PI*ZZ individuals develop severe liver disease that requires liver transplantation. Posttransplant survival is excellent. The largest burden of advanced liver disease lies within the adult population rather than children. Evaluation of lung function in adults before transplant is essential because of the underlying risk for chronic obstructive pulmonary disease. Post –liver transplantation lung function should also be monitored for decline. Although uncommon, cas...
Source: Clinics in Liver Disease - Category: Gastroenterology Authors: Source Type: research
Human Gene Therapy , Vol. 0, No. 0.
Source: Human Gene Therapy - Category: Genetics & Stem Cells Authors: Source Type: research
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