Left Ventricular Noncompaction (LVNC)

Excessive trabecular formation in the ventricular wall is a characteristic feature of left ventricular noncompaction (LVNC) which is a type of cardiomyopathy. It consists of two parts: the endocardial noncompaction layer and the epicardial compacted layer. We at Protheragen are a research service provider, that offers solutions for rare cardiovascular disorders research such as LVNC. Each project delivered through our distinct approach that combines strong disease models with therapeutic development is expertly innovative with exceptional quality.

Overview of Left Ventricular Noncompaction (LVNC)

Left ventricular noncompaction (LVNC) cardiomyopathy or "spongy myocardium" describes a defect stemming from an arrest in normal compaction processes of the myocardium, this is LVNC's cardiac abnormality during early embryonic development during the first trimester. Three features identify this condition: left ventricular trabeculations, recesses that communicate with the ventricular cavity, and an epicardial layer. These features may individually or in combination impair cardiac function, leading to cardiomyopathy.

In the case of LVNC cardiomyopathy symptoms, individuals present remarkable variability. They can go from having no symptoms to experiencing severe heart failure with thromboembolism, ventricular arrhythmia, or other sudden fatal events. LVNC cardiomyopathy incidence rates are: 0.81 per 100,000 for infants, 0.12 per 100,000 for children, and 50 per 100,000 for adults.

Fig.1 The embryological theory of LVNC. (Ogah, O. S., et al., 2023)

Pathogenesis of Left Ventricular Noncompaction (LVNC)

LVNC can be either sporadic or familial. Numerous genetic defects have been linked with the pathogenesis of LVNC. The genetic disorders are usually restricted and demonstrate heterogeneity. The mutations linked with LVNC comprise TTN, HCN4, LIM domain binding protein 3 (ZASP/LDP3), MYH7, RYR2, lamin A/C (LMNA), SCN5A, DTNA, and genes of sarcomere proteins, Tafazzin (TAZ).

Fig.2 Processes of the ventricle trabeculation and compaction stage. (Hirono, K., and Ichida, F., 2022)

Therapeutics Development for Left Ventricular Noncompaction (LVNC)

Currently, there is no definitive therapy for LVNC, and the focus is on managing symptoms, particularly thromboembolic complications and possibly life-threatening arrhythmia risks.

Our Services

Having specialized skills in molecular research and genetic engineering, we provide an all-inclusive approach regarding drug discovery and development which guarantees that the clients are provided with sophisticated diagnostic and therapeutic development systems. Our full range of services includes all facets of preclinical research, starting from the creation of the disease model to intricate studies of pharmacokinetic, and determination of drug safety levels.

Therapeutic Development Services

Diverse Platforms

• Small Molecule Drug Development
• Gene Therapy Development
• Therapeutic Peptide Development

• Cell Therapy Development
• Therapeutic Antibody Development
• Therapeutic Protein Development

Animal Model Development for LVNC

LVNC animal models assist in understanding the mechanisms and pathways available for achieving therapy as they are invaluable in providing steps used to solve cardiovascular problems. Among the other services our company offers, we specialize in the development of animal models for LVNC and other rare cardiovascular syndromes while integrating advanced technologies and thorough validation procedures.

Genetically Engineered Animal Model

The LVNC genetically engineered animal model is developed by manipulating cardiac developmental genes to induce an incompletely compacted left ventricular myocardium, effectively mimicking the human disease.

Optional models:

• Dtna^N49S model
• Other models

• Nkx2-5 deletion model

Taking advantage of cutting-edge technologies and comprehensive scientific approaches, Protheragen strives to mitigate the challenges of rare cardiovascular conditions through effective solutions. Therapy precision and excellent focus allow us to extend support to researchers and pharmaceutical partners surpassing the complex drug research. If you would like to know more, reach out to us.

References

• Hirono, Keiichi, and Fukiko Ichida. "Left ventricular noncompaction: a disorder with genotypic and phenotypic heterogeneity-a narrative review." Cardiovascular diagnosis and therapy 12.4 (2022): 495-515.
• Ogah, O S et al. "Left ventricular noncompaction cardiomyopathy: a scoping review." Annals of Ibadan postgraduate medicine 21.2 (2023): 8-16.