Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare and severe restrictive cardiomyopathy. Our company is committed to developing cutting-edge diagnostics and therapeutics for managing ATTR-CM. As your reliable partner in ATTR-CM research, we offer streamlined and comprehensive solutions to meet all your scientific research requirements.
Introduction to ATTR-CM
ATTR-CM is a rare and potentially fatal disease of the heart muscle that is characterized by the abnormal accumulation of misfolded transthyretin protein in various organs, including the heart. This condition can result in the development of heart failure or abnormalities in the conduction system of the heart. ATTR-CM is relatively rare, with an estimated annual incidence rate of around 3.6 cases per 100,000 individuals.
Fig. 1 The mechanism of transthyretin (TTR) protein dissociation, misfolding, and aggregation as amyloid fibrils. (Ruberg, Frederick L., et al., 2019)Pathogenesis of ATTR-CM
ATTR-CM can be classified into two primary types: hereditary ATTR-CM (hATTR-CM) and wild-type ATTR-CM (wATTR-CM). These two types have distinct pathogenic mechanisms.
Hereditary ATTR-CM (hATTR-CM)
This form of the disease is caused by genetic variants in the transthyretin gene. These variants lead to the production of abnormal transthyretin protein, which subsequently accumulates as amyloid deposits in the heart and other organs. hATTR-CM can be inherited within families and has been associated with specific variants in different populations worldwide.
Wild-type ATTR-CM (wATTR-CM)
Unlike hATTR-CM, wATTR-CM occurs in individuals without genetic variants in the transthyretin gene. The exact mechanisms underlying the development of wATTR-CM are still under investigation. However, it is believed that age-related changes in transthyretin protein structure and metabolism contribute to the formation of amyloid deposits predominantly in the heart.
Types of ATTR-CM Therapy
Small Molecule Therapies
Small molecule therapies primarily focus on stabilizing transthyretin or inhibiting the formation of amyloid. Tafamidis is a small molecule that acts as a transthyretin stabilizer. Tafamidis binds to transthyretin, stabilizing its natural tetrameric structure and preventing its misfolding and aggregation into harmful amyloid fibrils.
Antisense Oligonucleotide (ASO) Therapy
ASO can be specifically designed to target and decrease the production of abnormal transthyretin. Patisiran and Inotersen are ASOs that bind to transthyretin messenger RNA (mRNA), causing its degradation and reducing abnormal protein synthesis.
Gene Therapy
Gene therapy involves the delivery of therapeutic genes or RNA molecules to modulate transthyretin expression. By correcting the genetic defect in hATTR-CM, gene therapy offers the possibility of long-term disease relief and even potential cure. Several gene therapy strategies are in the research phase and have shown promise in animal models.
Our Services
Our company has established comprehensive platforms for developing rare disease diagnostics and therapies, encompassing small molecule drug, cell therapy, gene therapy, therapeutic antibody, therapeutic peptide, and therapeutic protein. Through our dedicated platforms, we are fully devoted to advancing the development of innovative diagnostic tools and therapies for ATTR-CM.
Recognizing the significance of animal disease models in the therapy development for ATTR-CM, we offer our expertise in establishing animal models specifically tailored for ATTR-CM. These models serve as invaluable tools to facilitate the safety evaluation and pharmacokinetics study of your drug candidates.
Animal Models of ATTR-CM
| Inoculation Models | |||
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| At our company, our scientists introduce misfolded transthyretin aggregates or amyloid fibrils directly into animals to study the spread of amyloid and its impact on the heart. | |||
| Genetically Engineered Models | |||
| Our scientists have demonstrated expertise in developing genetic engineering models for ATTR-CM. Leveraging the cutting-edge CRISPR/Cas9 gene editing technology and transgenic methods, they have achieved significant success in generating both knock-in and transgenic models of ATTR-CM. | |||
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| Optional Species | D. Melanogaster, C. Elegans, Mice, Rats, Non-human Primates (Monkeys), Others | ||
If you are interested in our services, please don't hesitate to contact us for more information and a detailed quotation regarding the specific services you require.
References
- Ruberg, Frederick L., et al. "Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review." Journal of the American College of Cardiology 73.22 (2019): 2872-2891.
- Ibrahim, Ridwan Babatunde, et al. "Contributions of animal models to the mechanisms and therapies of transthyretin amyloidosis." Frontiers in Physiology 10 (2019): 441908.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.