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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ConclusionsLung and liver transplantation in AATD patients are associated with very good long-term survival rates that are comparable to, and sometimes superior to, other transplant indications. Although not currently recommended in AATD, LVRS may have a role in a minority of patients. The value of Alpha 1 Antitrypsin (AAT) augmentation therapy following lung transplantation requires further study. Wherever possible, AAT therapy should be continued in the period around elective surgeries.SummaryAlthough AATD is a widely discussed and researched topic in the literature, surgical intervention for AATD, in addition to the man...
Source: The American Journal of Surgery - Category: Surgery Source Type: research
A 62-year old non-smoker, Caucasian male was evaluated for lung transplantation based on severe upper-lobe predominant emphysema with superimposed fibrosis in the lower lung zones (Figure 1). The patient had no significant exposure history, and prior work-up for alpha-1-antitrypsin deficiency, autoimmune disease, and hypersensitivity pneumonitis was unremarkable. The diagnosis of Niemann Pick disease, type B was eventually established based on a compatible family history with an almost identical disease presentation in a sibling.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: Case Anecdotes, Comments and Opinions Source Type: research
Authors: Hsin MKY, Wong CF, Yan SW, Fan KY, Ho CKL, Bhatia I, Au TWK Abstract Clinical lung transplant was first performed in Hong Kong in 1995. In the early years, the volume of activity was very low. There has been a clear trend of increasing volume in the past few years. The recipient pathology is very different from the International Society for Heart and Lung Transplantation (ISHLT) database, with complete absence of cystic fibrosis and alpha-1-antitrypsin deficiency, and a predominance of diseases of the pulmonary circulation. Lymphangioleiomyomatosis (LAM) has a much higher representation on the waiting list...
Source: Journal of Thoracic Disease - Category: Respiratory Medicine Tags: J Thorac Dis Source Type: research
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
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