Congenital Heart Block
In women with anti-Ro/La autoantibodies, maternal autoantibody placental transfer may disrupt fetal atrioventricular conduction, leading to congenital heart block in the fetus. At Protheragen, we offer targeted advanced research services on rare cardiovascular diseases such as congenital heart block. Moreover, we appreciate the particular issues posed by these diseases and strive to be at the forefront of innovation in drug development and discovery.
Introduction to Congenital Heart Block
Autoimmune congenital heart block is an immune-mediated condition featuring complete heart block caused by maternal anti-Ro/SSA and anti-La/SSB autoimmune antibodies. The frequency of congenital heart block is estimated to be one in twenty thousand among fetuses and/or newborns of women possessing autoantibodies against 48-kDa SSB/La and 52-kDa SSA/Ro and 60-kDa SSA/Ro.
Fig.1 Prenatal management of immune-associated bradycardia. (Liao, H., et al., 2021)Pathogenesis of Congenital Heart Block
Clearance of apoptotic cardiomyocytes is done by resident cardiomyocytes in early fetal development. In the case of individuals suffering from anti-Ro/SSA and/or anti-La/SSB, these antibodies may complex with the SSA and SSB antigens bound to the apoptotic cardiomyocytes. Such immune complex formation makes the physiological clearance of apoptotic cardiomyocytes impossible. Subsequently, macrophages engulf the apoptotic cardiomyocytes that have been bound to immune complexes through Fcγ receptors. Afterward, the macrophages are activated to produce proinflammatory mediators such as TGF-β and TNF-α which induce fibroblasts to differentiate into myofibroblasts and subsequently result in scarring.
Fig.2 Pathogenesis, prevention, and therapy of congenital heart block. (Liao, H., et al., 2021)Therapeutics Development for Congenital Heart Block
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Hydroxychloroquine | Suppress immune response by diminishing Toll-like receptor activation and the secretion of cytokines. | Toll-like receptor | NCT01379573 | Phase II |
| Intravenous immunoglobulin | Intervene by neutralizing maternal autoantibodies so that congenital heart block does not advance further. | / | NCT00460928 | Phase I |
| Dexamethasone | Attach to intracellular glucocorticoid receptors, and reduce the production of pro-inflammatory cytokines and other mediators. | GR | NCT00007358 | N/A |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a therapy plan recommendation. For guidance on therapy options, please visit a regular hospital.
Our Services
The integrative approach makes it possible to facilitate the transition from the discovery phase to the developmental stage of research, saving time. Our professionals dedicate themselves to the advancement of diagnostics, therapeutics, and disease model development, ensuring that every single project is completed to the highest scientific standards. Besides the primary focus on developing new diagnostic and therapy methodologies, we also offer specialized services in pharmacokinetics and drug safety evaluation.
Therapeutic Development Services
Diverse Platforms
Animal Model Development for Congenital Heart Block
Animal models are essential in the study of rare cardiovascular disease and offer helpful information which is vital for crafting therapy methods. We focus on developing custom animal models designed to aid research in congenital heart block.
Induced Animal Model Development
The passive transfer of autoantibodies or active immunization strategies are implemented that induce offspring with features of congenital heart block.
Optional models:
- Induced model using anti-p200 monoclonal antibodies.
- Experimental mouse model created via passive transfer of human autoantibodies into pregnant mice.
- Other models
It is the combination of teamwork and innovation that steers us not only to succeed but also to remain ahead in the cardiovascular research industry. With our state-of-the-art knowledge and facilities, Protheragen strives to spearhead therapy development and integrate ourselves as contributors toward the betterment of individuals with exceptional and harsh cardiovascular ailments. If you are interested in our services, please contact us.
References
- Huang, Ying et al. "Autoimmune congenital heart block: a case report and review of the literature related to pathogenesis and pregnancy management." Arthritis research & therapy 26.1 (2024): 8.
- Liao, Hongyu et al. "Prenatal Management Strategy for Immune-Associated Congenital Heart Block in Fetuses." Frontiers in cardiovascular medicine 8 (2021): 644122.
For research use only, not for clinical use.