ArticleThe Journal of clinical investigation2014
Antisense oligonucleotide treatment ameliorates alpha-1 antitrypsin-related liver disease in mice.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 80 citations in OpenAlex.
- Autocrine Netrin-1 Signaling in Hepatic Stellate Cells Drives Liver Fibrosis and Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A compact base editor rescues AATD-associated liver and lung disease in mouse models.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- A cure for alpha-1? Novel therapeutics in alpha-1 antitrypsin deficiency.The European respiratory journal · 2025Article
- Chaperone-mediated autophagy degrades SERPINA1Autophagy · 2025Article
- A1AT dysregulation of metabolically stressed hepatocytes by Kupffer cells drives MASH and fibrosis.Experimental & molecular medicine · 2025Article
- Exosome-associated miRNA-99a-5p targeting BMPR2 promotes hepatocyte apoptosis during the process of hepatic fibrosis.Clinical and experimental medicine · 2023Article
- Future Perspectives in the Diagnosis and Treatment of Liver Disease Associated with Alpha-1 Antitrypsin Deficiency.GE Portuguese journal of gastroenterology · 2023Review
- Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.Bioengineering (Basel, Switzerland) · 2022Review
- Alpha-1-Antitrypsin Deficiency.Clinical liver disease · 2022Review
- Development of a small molecule that corrects misfolding and increases secretion of Z αEMBO molecular medicine · 2021Article
- Liver disease with unknown etiology - have you ruled out alpha-1 antitrypsin deficiency?Therapeutic advances in chronic disease · 2021Review
- Alpha-1 antitrypsin deficiency liver disease.Translational gastroenterology and hepatology · 2021Review
- Advances in Alpha-1 Antitrypsin Gene Therapy.American journal of respiratory cell and molecular biology · 2020Review
- Alpha-1 Antitrypsin Deficiency-Mediated Liver Toxicity: Why Do Some Patients Do Poorly? What Do We Know So Far?Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
- Leveraging Population Genomics for Individualized Correction of the Hallmarks of Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
- Update on Alpha-1 Antitrypsin Deficiency in Liver Disease.Clinical liver disease · 2020Review
- Fetal antisense oligonucleotide therapy for congenital deafness and vestibular dysfunction.Nucleic acids research · 2020Article
- Prognostic Significance of Elevated Preoperative Serum CA125 Levels After Curative Hepatectomy for Hepatocellular Carcinoma.OncoTargets and therapy · 2020Article
- Article
- Don't Miss the BoAAT: Correctly Diagnosing Acute-on-Chronic Liver Disease.Digestive diseases and sciences · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disease that results from mutations in the alpha-1 antitrypsin (AAT) gene. The mutant AAT protein aggregates and accumulates in the liver leading to AATD liver disease, which is only treatable by liver transplant. The PiZ transgenic mouse strain expresses a human AAT (hAAT) transgene that contains the AATD-associated Glu342Lys mutation. PiZ mice exhibit many AATD symptoms, including AAT protein aggregates, increased hepatocyte death, and liver fibrosis. In the present study, we systemically treated PiZ mice with an antisense oligonucleotide targeted against hAAT (AAT-ASO) and found reductions in circulating levels of AAT and both soluble and aggregated AAT protein in the liver. Furthermore, AAT-ASO administration in these animals stopped liver disease progression after short-term treatment, reversed liver disease after long-term treatment, and prevented liver disease in young animals. Additionally, antisense oligonucleotide treatment markedly decreased liver fibrosis in this mouse model. Administration of AAT-ASO in nonhuman primates led to an approximately 80% reduction in levels of circulating normal AAT, demonstrating potential for this approach in higher species. Antisense oligonucleotides thus represent a promising therapy for AATD liver disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.