Alnylam begins ALN-AAT’s Phase I / II trial for alpha-1 liver disease

Alnylam Pharmaceuticals has started the Phase I / II clinical trial with ALN-AAT, a subcutaneously administered investigational RNAi therapeutic targeting alpha-1 antitrypsin (AAT) to treat AAT deficiency-associated liver disease (alpha-1 liver disea…
Source: Drug Development Technology - Category: Pharmaceuticals Source Type: news

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Conclusion: Our data reveal molecular epigenetic signatures within this mutationally homogeneous group that point to ways to stratify patients for liver disease risk.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by array Homo sapiens Source Type: research
Conclusions: While there is a certain overlap between the results of the current study and published transcriptomic profiles of non-transplanted livers with steatosis, we have identified discrete characteristics of the non-alcoholic fatty liver disease in liver grafts potentially utilizable for the establishment of predictive signature. Introduction Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries, its prevalence being estimated at 19–31.3% (1). It encompasses a range of conditions that are thought to arise from fatty liver (simple steatosis) throu...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
α1-Antitrypsin deficiency (AATD) is an inherited disease characterized by emphysema and liver disease. AATD is most often caused by a single amino acid substitution at position 342 in the mature protein, resulting in the Z mutation of the AAT gene (ZAAT). This substitution is associated with misfolding and accumulation of ZAAT in the endoplasmic reticulum (ER) of hepatocytes, causing a toxic gain of function. ERdj3 is an ER luminal DnaJ homologue, which, along with calreticulin, directly interacts with misfolded ZAAT. We hypothesize that depletion of each of these chaperones will change the fate of ZAAT polymers. Our...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Cell Biology Source Type: research
Discussion The liver is one of the largest organs in the body, weighing just over 3 pounds in an adult. It is found in the upper right abdomen, under the right dome of the diaphragm. Grossly, it has asymmetric lobes with the right being larger than the left. The lobes are separated by a fibrous connective tissue band that also anchors the liver in the abdominal cavity. The gallbladder is located on the inferior surface of the liver and stores bile, which is then released into the duodenum. Microscopically, the liver cells are arranged in lobules with canals carrying blood vessels and bile ducts. At any moment about 10-13% ...
Source: - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Abstract Orthotopic liver transplantation, rather than drug therapy, is the major curative approach for various inherited metabolic disorders of the liver. However, the scarcity of donated livers is a serious problem. To resolve this, there is an urgent need for novel drugs to treat inherited metabolic disorders of the liver. This requirement, in turn, necessitates the establishment of suitable disease models for many inherited metabolic disorders of the liver that currently lack such models for drug development. Recent studies have shown that human induced pluripotent stem (iPS) cells generated from patients with...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research
Alpha-1 antitrypsin deficiency (AATD) is a common but under-recognised genetic condition that affects approximately 1 in 2000 to 1 in 5000 individuals and predisposes to early-onset emphysema and liver disease [1]. Alpha-1 antitrypsin (AAT) is mainly produced in the liver, and its main function is to protect the lung against proteolytic damage, especially from neutrophil elastase [2]. To date, more than 100 variant alleles of the AAT gene (SERPINA1) have been described, but the Z allele is the most prevalent and responsible for severe AATD leading to lung and liver disease [3].
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Editorials Source Type: research
AbstractBackgroundThe proportion of adults with liver disease due to severe alpha-1-antitrypsin deficiency (AATD), with PiZZ phenotype, is not clear. The markers of the AATD liver disease, how it progresses, and measures for its prevention have not been established. The aim of this study was to analyze the risk of liver disease in individuals with severe AAT deficiency (PiZZ).MethodsLongitudinal clinical and laboratory data were obtained from the Swedish National registers, by cross-linkage between the Swedish national AATD register, the Swedish National Patient Register, the National Cancer Register and the National Cause...
Source: Journal of Gastroenterology - Category: Gastroenterology Source Type: research
Abstract A female patient was first seen at age 65 due to a diagnosis of alpha-1-antitrypsin deficiency (AATD). She was a lifelong non-smoker, with no significant history of second hand smoke exposure. There was no prior family history of AATD or liver disease. Her serum AAT concentration was measured on two occasions and in both cases, concentration was
Source: Clinical Biochemistry - Category: Biochemistry Authors: Tags: Clin Biochem Source Type: research
Condition:   ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease Interventions:   Drug: ALN-AAT02;   Drug: Placebo Sponsor:   Alnylam Pharmaceuticals Not yet recruiting
Source: - Category: Research Source Type: clinical trials
More News: Alpha-1 Antitrypsin Deficiency | Clinical Trials | Liver | Liver Disease | Pharmaceuticals | Urology & Nephrology