Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy with fibrofatty substitution of the myocardium which is associated with ventricular arrhythmias, ventricular dysfunction, and even sudden cardiac death. Protheragen is a technological leader in providing drug development services for rare cardiovascular disorders like ARVC and is dedicated to offering comprehensive support to scientists and researchers working in this area.

Introduction to Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

ARVC is a primary cardiomyopathy seen form of cardiomyopathies, which is normally diagnosed after the individual presents with findings of arrhythmia. It is estimated to have a prevalence rate of 1 in 2000-5000 individuals and with a male preponderance. Initial ARVC case reports centered on the pathology of the right ventricle, but in recent years there has been stronger evidence for biventricular involvement with the minority being partial forms of left or right-side ventricle involvement.

Fig.1 Four phases classically described in ARVC. (Tadros, H. J., et al., 2023)

Pathogenesis of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

ARVC is characterized by fibrofatty replacement of the ventricular myocardium due to specific mutations that culminate into ventricular arrhythmias and sudden cardiac death. Eight genes account for the majority of pathogenic or likely pathogenic variants in ARVC which include five desmosomal genes PKP2, DSP, DSG2, DSC2, JUP, and three non-desmosomal genes TMEM43, DES, and PLN which carry the greatest evidence for causation of ARVC. It is believed deep alteration in genes encoding desmosomal proteins explains 50% to 60% of all ARVC cases.

Fig.2 Genes related to arrhythmogenic cardiomyopathy. (Gerull, B., and Brodehl, A., 2020)

Therapeutics Development for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

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

Protheragen collaborates with academic institutions, pharmaceutical organizations, and innovators to form strategic alliances that enhance our research capacity and accelerate the conversion of scientific discoveries into actual therapies. These comprehensive solutions encompass diagnostic and therapeutic services and even the creation of disease models. This integrated service approach greatly streamlines the research process, thus conserving time and resources.

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 Services

In vivo models play a critical role in designing interventions for uncommon cardiovascular conditions like ARVC. Here at our company, we are dedicated to providing personalized animal model development services that enhance researchers' ability to diagnose and treat this difficult disease.

Genetically Engineered Models

• Ryr2 knockout model
• Lbd3 knockout model
• Dsp knockout model

• Pkp2 knockout model
• Jup knockout model
• Other models

Given the distinct complexities of rare cardiovascular diseases like ARVC, Protheragen customizes our research approaches to deal with particular gaps and unmet needs. Together with our clients we deep dive in to develop and assess novel therapeutic agents for ARVC, offering services such as pharmacodynamics, pharmacokinetics, safety review, and analysis. For detailed requests and sophisticated estimates for the required services, feel free to contact us.

References

• Tadros, Hanna J et al. "The Many Faces of Arrhythmogenic Cardiomyopathy: An Overview." The application of clinical genetics 16 (2023): 181-203.
• Gerull, Brenda, and Andreas Brodehl. "Genetic Animal Models for Arrhythmogenic Cardiomyopathy." Frontiers in physiology 11 (2020): 624.