Tangier Disease (TD)
Tangier disease (TD), also known as Tangier's disease or α-lipoprotein deficiency, is an autosomal recessive genetic disorder. It is caused by a defect in α-lipoprotein synthesis, leading to the accumulation of cholesterol esters in the reticuloendothelial system, intestinal mucosa, and skin. At our company, we have assembled a team of seasoned professionals with a wealth of experience in navigating drug and therapy development challenges specific to Tangier Disease.
Introduction to Tangier Disease
Tangier disease is a rare genetic disorder inherited in an autosomal recessive pattern, marked by abnormally low levels of high-density lipoprotein (HDL) cholesterol in the bloodstream. This condition arises from mutations in the ABCA1 gene, which is essential for the transfer of cholesterol from cells to HDL particles. As a result, cholesterol accumulates in several tissues, notably the tonsils, liver, spleen, and lymph nodes. With around 200 cases documented globally, Tangier disease is exceptionally uncommon.
Pathophysiology of Tangier Disease
Tangier disease results from mutations in the ABCA1 gene, which is vital for moving cholesterol and phospholipids from cells to create new high-density lipoprotein particles. These genetic defects disrupt the normal process of cholesterol removal from cells, causing cholesterol to build up in different tissues. This accumulation leads to distinctive features such as orange-hued tonsils, enlargement of the liver and spleen, and peripheral nerve damage. The significantly lower HDL cholesterol levels seen in Tangier disease increase the likelihood of developing atherosclerosis and cardiovascular conditions.
Fig. 1 Roles of ABCA1 in formation of HDL particle. (Koseki, M., et al., 2021)Genetic Testing Development of Tangier Disease
Whole-exome sequencing (WES) has emerged as a crucial tool for diagnosing Tangier disease. WES involves sequencing the exons, the coding regions of genes, to identify pathogenic variants in the ABCA1 gene. A recent study identified a novel homozygous variant in an individual using WES, underscoring the importance of combining WES with bioinformatic tools such as Mutation Taster and DANN for pathogenicity prediction. Additionally, bioinformatic models, like those generated by SWISS-MODEL, help illustrate how these mutations affect protein structure and function.
Therapeutics Development of Tangier Disease
| Class | Drug | Target | NCT | Phase |
|---|---|---|---|---|
| Niacin | Niacin | LXR | NCT 00120289 | Phase Ⅲ |
| Glitazones | Pioglitazone | PPARγ | NCT00700856 | |
| Fibric acid derivatives | Fibric acid | PPARα | NCT00000620 | Phase Ⅲ |
| Fibric acid derivatives | Pemafibrate | PPARα | NCT03071692 | Phase Ⅲ |
Our Services
Our company adopts a collaborative approach, partnering closely with clients to create tailored and innovative therapy strategies for TD. We offer comprehensive support throughout the entire development process, ensuring effective and customized solutions.
Platforms of Tangier Disease Therapy Development
Animal Models of Tangier Disease
We have considerable expertise in developing and employing animal models that accurately replicate the disease characteristics and therapeutic responses seen in Tangier Disease. These models are instrumental in investigating the underlying mechanisms of Tangier Disease and assessing the safety and effectiveness of prospective therapies with precision.
Non-Genetically Engineering Models
They are biological systems used in research that do not involve the manipulation or alteration of an organism's genetic material.
Optional Models: High-Cholesterol Diet Model
Genetically Engineering Models
Genetically engineering models involve the manipulation of genetic material to study specific disease mechanisms and therapeutic interventions.
Optional Models: ABCA1 KO Mice Model; Human ABCA1 Transgenic Mice Model
Moreover, we provide a variety of detailed animal model services focused on particular signaling pathways and molecular targets.
If you are interested in our services, please don't hesitate to contact us.
References
- Koseki, M., et al., "Current Diagnosis and Management of Tangier Disease." J Atheroscler Thromb, (2021). 28(8): p. 802-810.
- Ramasamy, I., "Update on the molecular biology of dyslipidemias." Clin Chim Acta, (2016). 454: p. 143-185.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.