Alpha-1 Antitrypsin Deficiency (A1AD)
Alpha-1 antitrypsin deficiency, or A1AD, is a chromosomal anomaly that alters the synthesis of alpha-1 antitrypsin AAT proteins within the liver. The backbone of this disorder is it increases the chances of developing various lung and liver diseases. Our company does its utmost in tackling rare diseases like A1AD and serves researchers in the sector with all required services.
Overview of A1AD
A1AD is a rare inherited disorder that has an occurrence frequency of nearly 1 in 10,000. What differentiates A1AD from other disorders is the deficiency of alpha-1 antitrypsin (AAT) in patients. The AAT protein, critically important for the human body, is produced in the liver and protects the lungs from being damaged by enzymes, and most importantly, from neutrophil elastase. A1AD is caused by mutation in the SERPINA1 gene, which is responsible for the synthesis of AAT. Such mutations result in reduced expression, abnormal folding, or excessive AoT protein build-up which can impair the action of AAT proteins.
Fig.1 Pathophysiology and therapy approachesfor A1AD. (Fromme, M., et al., 2022)
Pathogenesis of A1AD
Unlike with emphysema and other obstructive lung diseases, the pathogenesis of A1AD stems from the lungs because of the imbalance between proteases and their inhibitors. The lack or dysfunctional AAT protein in A1AD cases is inadequate to modulate the operational levels of the proteases, resulting in the lung tissue being standardly destroyed and ultimately leading to severe chronic obstructive pulmonary disease. A1AD primarily affects the lungs but, can also manifest in the liver. Within the liver, abnormal accumulation of AAT proteins can lead to inflammatory conditions, fibrosis, and, in severe 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
Quantifying AAT in blood, as low levels of this are associated with deficiency, while also evaluation of C-reactive protein should be performed as AAT is an acute phase protein.
Gene Detection
Confirmatory genetic testing usually focuses on some specific mutations in the SERPINA1 and assesses possible disease progression risks in the patient as well as in 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
Lung-related diseases can be dealt with using bronchodilators, inhaled corticosteroids, and even antibiotics due to their ability to control symptoms and circumvent disease complications. Thus, carbamazepine and rapamycin have also been found to aid in improving autophagy.
Gene Therapy
Currently available literature focuses on the treatment of A1AD using gene therapeutics including the application of the CRISPR/Cas9 system or the use of interference RNA to ameliorate the defecting gene or increase the rate of clearance of the abnormal AAT proteins.
Our Services
We offer vital assistance for rare diseases such as A1AD. With the help of our animal models, researchers studying A1AD are supported throughout the entire process, from animal models to a fully developed therapeutic. It is because of our team of experts, innovative therapeutic technologies are constructed. They are world-famous professionals who have spent years researching A1AD and other rare diseases.
Therapy Development Platforms
Animal Models of A1AD
Animal models are essential for understanding A1ADs mechanisms and developing therapeutics to target them. At our company we offer multiple animal models for the study of different pathogenesis of A1AD and other possible therapeutic approaches.
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.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.