Alpha-1 Antitrypsin Deficiency (A1AD)
Alpha-1 antitrypsin deficiency (A1AD) is a genetic disorder that affects the production of a protein called alpha-1 antitrypsin (AAT) in the liver. This deficiency leads to a higher risk of developing lung and liver diseases. Our company excels in the field of rare diseases, including A1AD, and provides comprehensive services for researchers in this area.
Overview of A1AD
A1AD, a rare hereditary affliction boasting an incidence rate of about 1-5 cases per 10,000 individuals, is distinguished by plummeting levels of plasma AAT. AAT, an indispensable protein synthesized in the liver, plays a pivotal role in preserving lung integrity through the prevention of enzymatic harm, especially via neutrophil elastase. A1AD occurs when there is a mutation in the SERPINA1 gene, which provides instructions for producing AAT. This mutation can lead to a decreased production, misfolding, or accumulation of abnormal AAT proteins, affecting their release into the bloodstream.
Fig.1 Pathophysiology and therapy approachesfor A1AD. (Fromme, M., et al., 2022)
Pathogenesis of A1AD
The pathogenesis of A1AD involves an imbalance between proteases (enzymes that break down proteins) and their inhibitors, particularly in the lungs. In A1AD, the reduced levels or dysfunctional AAT protein fail to adequately control the activity of proteases, leading to the destruction of lung tissue, which can result in chronic obstructive pulmonary disease, emphysema, and bronchiectasis. In addition to lung disease, A1AD can also affect the liver. Abnormal AAT proteins can accumulate within liver cells, causing liver inflammation, fibrosis, and, in some cases, cirrhosis.
Fig.2 A1AD genotypes and factors promoting the development of A1AD-related liver disease. (Fromme, M., et al., 2022)Diagnostics Development of A1AD
AAT Quantification
Measures the level of AAT in the blood, which low levels may indicate a deficiency. Additionally, it is important to evaluate the C-reactive protein level, as AAT can potentially increase during inflammation.
Gene Detection
Identifying specific mutations in the SERPINA1 gene through genetic testing can confirm the diagnosis and help assess the risk of disease progression for the individual and their family members.
Biomarker
In addition, some specific biomarkers can accurately predict disease progression and evaluate therapeutic effects, such as circulating polymers, Aa-Val360, desmosine, and isodesmosine.
Therapeutics Development of A1AD
Small Molecule Drug Therapy
Various drugs, such as bronchodilators, inhaled corticosteroids, and antibiotics can manage symptoms and prevent complications associated with lung disease. Carbamazepine and rapamycin have been found to improve autophagy.
Gene Therapy
In recent years, research has focused on gene therapy as potential therapeutics for A1AD, such as using CRISPR/Cas9 system or interference RNA to correct the underlying genetic defect or enhance the clearance of abnormal AAT proteins.
Our Services
Our team of experts consists of renowned researchers and professionals who possess extensive knowledge and experience in rare diseases, enabling us to provide invaluable insights and support to researchers studying A1AD, with our animal models and therapeutic development platform to help you accelerate the development of novel therapies for rare diseases like A1AD.
Therapy Development Platforms
Animal Models of A1AD
Animal models provide valuable insights into the mechanisms underlying A1AD and can be used to develop new therapeutics and therapies for the condition. Our company can provide a variety of animal models to help you understand the pathogenesis of A1AD and explore potential therapeutic strategies.
Chemical-induced Models
Chemical-induced animal models of A1AD involve the use of specific chemicals or substances to induce lung or liver injury that mimics the characteristics of A1AD.
Optional Models: Elastase-induced model; LPS-induced model, etc.
Genetically Engineered Models
The genetic engineering animal model of A1AD involves the creation of transgenic mice or other organisms with genetic modifications that mimic the disease characteristics seen in humans.
Optional Models: Serpina1btm1Jti model; IL-13 overexpression model, etc.
Why Choose Us
With our comprehensive services, expertise, and collaborative approach, we provide comprehensive services including pharmacokinetic studies and drug safety evaluation, and are committed to making significant contributions to the understanding, diagnosing, and treating of rare diseases.
If you are interested in learning more about our services and how we can support your research endeavors, please do not hesitate to reach out to us for further information.
References
- Fromme, Malin et al. "Alpha-1 antitrypsin deficiency: A re-surfacing adult liver disorder." Journal of hepatology 76.4 (2022): 946-958.
- Cortes-Lopez, et al. "Alpha-1 Antitrypsin Deficiency: a Rare Disease?" Current allergy and asthma reports 20.9 (2020): 51.
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