Carney Complex

Carney complex represents a rare hereditary tumoral condition linked to either one of the multiple endocrine neoplasia syndromes (MEN) or primary pigmented nodular adrenal dysplasia (PPNAD). Of all the potentially mortal complications associated with Carney complex, the most pronounced risk, accounting for 57% of mortality, deals with cardiac myxomas and ensuing complications from cardiac surgery. Protheragen is a provider of comprehensive drug research and development services aimed at addressing critical unmet needs in rare cardiovascular diseases. Our core expertise is providing end-to-end support for disorders such as Carney complex.

Introduction to Carney Complex

The Carney complex is marked by skin pigmentary abnormalities, myxomas, Schwannomas, and endocrine tumors or overactivity of them. The most prevalent feature of the Carney complex is pale brown to black lentigines, which increase in number during puberty. In individuals with Carney complex, about 20% to 40% have cardiac myxomas, which occur early in life and can be present in one or more of the cardiac chambers. Cardiac myxomas manifest with symptoms due to intracardiac flow obstruction, such as blood flow stagnation or embolism (to peripheral systemic arteries) and/or heart failure. Sudden death may occur in cases where a myxoma fully obstructs a valve opening.

Fig.1 PKA Pathway in Carney complex. (Schernthaner-Reiter, et al., 2016)

Pathogenesis of Carney Complex

Carney complex is considered to have an autosomal dominant inheritance pattern, but it is now associated with two different genetic loci. One of the loci is the CNC gene 1, which constitutes a germline mutation in the regulatory subunit 1A of protein kinase A (PRKAR1A) located at 17q22-24, which can be found in roughly two-thirds of Carney complex individuals. Roughly seventy percent of individuals with Carney complex show parental transmission, while close to thirty percent present with a de novo pathogenic variant.

Fig.2 PRKAR1A gene and protein structure diagram. (Zheng, H., et al., 2024)

Therapeutics Development for Carney Complex

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

Through specializing in Carney complex, we help to develop innovative therapy for our clients by offering a one-stop solution. We offer comprehensive preclinical services from cutting-edge diagnostics and therapeutics to advanced disease models and rigorous testing. Every stage of the drug development process is carefully studied from discovery to late-stage evaluation.

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 Carney Complex

Comprehension of Carney complex and devising efficient interventions hinges on the availability of appropriate animal models. To accelerate your drug discovery and development programs for Carney complex, we collaborate with you to develop and construct custom animal models that mimic the distinct pathological features of Carney complex.

Genetically Engineered Animal Models

These models are designed to reflect certain genetic changes connected to the Carney complex, for example, alterations in the PRKAR1A gene.

• PRKAR1A Knockout Model

• Other models

Pharmacokinetics and Drug Safety Research Services

Pharmacokinetic Research Services

• Physiochemical Studies
• In Vitro Metabolism Studies
• In Vitro Permeability and Transporter Studies
• Drug Absorption Studies
• Quantitative Tissue Distribution Studies
• Bioavailability Studies
• Metabolite Profiling and Identification Studies
• Mass Balance Studies
• Biliary Excretion Studies

Drug Safety Research Services

• General Toxicology Evaluation
• Genetic Toxicology Evaluation
• Developmental and Reproductive Toxicity Evaluation
• Safety Pharmacology Evaluation
• Local Toxicity Evaluation
• Phototoxicity Evaluation
• Tissue Cross-Reactivity Evaluation
• Immunogenicity and Immunotoxicity Evaluation
• Toxicokinetics Evaluation

In conjunction with the development of animal models, Protheragen also offers integrated pharmacokinetic and safety evaluation studies of drugs. These critical services ensure that all potential drug candidates undergo absorption, distribution, metabolism, and excretion profiling along with appropriate safety and tolerability assessments. Provision of such comprehensive services de-risks our partners' programs, further enabling accelerated, overall streamlined processes in drug development. If interested in the offered services, do not hesitate to reach out.

References

• Schernthaner-Reiter, Marie Helene et al. "MEN1, MEN4, and Carney Complex: Pathology and Molecular Genetics." Neuroendocrinology 103.1 (2016): 18-31.
• Zheng, Huaqiang et al. "Novel PRKAR1A mutation in Carney complex: a case report and literature review." Frontiers in endocrinology 15 (2024): 1384956.