Gorlin's Syndrome

Gorlin's syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant genetic disorder that increases the risk of developing tumors, including cardiac fibromas. Protheragen, a leader in research services with a focus on rare cardiovascular diseases, offers fully integrated drug discovery and development services. We have scientific expertise and creativity in problem-solving, which enables us to deliver comprehensive solutions for Gorlin's syndrome from early-stage research to preclinical studies.

Introduction to Gorlin's Syndrome

Gorlin's syndrome manifests as an autosomal dominant condition occurring in 1 out of every 19,000 live births. Primarily, Gorlin's syndrome results from PTCH1 gene mutations, a tumor suppressor. People with this syndrome are prone to developing several cancers and noncancerous growths, including cardiac fibromas. Despite being benign, these tumors can lead to potentially life-threatening complications such as chest pain, congestive heart failure, arrhythmias, or even sudden death.

Fig.1 PTCH1 gene mutation sites and domain structure of Patched 1 protein. (Onodera, S., et al., 2020)

Pathogenesis of Gorlin's Syndrome

Gorlin's syndrome, often associated with a mutation in the PTCH1 gene, is an inherited disorder of an autosomal dominant pattern. The Patched-1 protein encoded by PTCH1 at the 9q22 chromosome is one of the membrane receptors on cell surfaces that activate Hedgehog signaling pathways. PTCH1 is a tumor suppressor that acts by inhibiting its target Smoothened (SMO), a central processor of the Hedgehog signal. A mutation or non-functional state of PTCH1 results in activation of the SMO pathway, unleashing uncontrolled effects downstream of the pathway. Unlimited activation leads to unregulated proliferation and differentiation, along with accompanying survival, contributing towards features of Gorlin's syndrome.

Fig.2 Intracardiac tumor in Gorlin syndrome. (Szczałuba, K., et al., 2020)

Therapeutics Development for Gorlin's Syndrome

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

Protheragen provides an integrated research service for this peculiar and complex condition, which includes diagnostics, therapeutics, and sophisticated disease modeling. We are able to develop specific diagnostic markers for the identification of cardiac fibromas, devise novel therapeutic interventions, and create dependable preclinical models that accurately reproduce the pathophysiology of the disease in question. This one-stop strategy ensures that all aspects of advanced research on Gorlin's syndrome will be addressed in an optimally efficient manner.

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 Gorlin's Syndrome

For the investigation of Gorlin's syndrome alongside effective therapeutic development, animal models are critical. Understanding the importance of accurate and meaningful models, we provide specialized services concerning the development of animal models for Gorlin's syndrome. With our specialized knowledge, we are capable of creating and generating custom animal models that mimic the disease's particular features relevant to your research goals.

Genetically Engineering Animal Model

Genetically engineered models for Gorlin's syndrome typically feature targeted deletions or mutations in the Ptch1 gene to closely replicate the genetic basis and phenotypic manifestations of the human disorder.

Optional models:

• Ptch1 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

Protheragen's comprehensive service platform contains pharmacokinetics and drug safety studies critical for wellness, compliance, and regulatory submission. We provide an integrated research solution with these services that is seamless and compliant. Our constant focus on scientific rigor and state-of-the-art methods makes us a favored partner among scholars and biotechnological companies seeking to develop safe and effective therapeutics for uncommon cardiovascular diseases. For other inquiries regarding our services, contact us directly.

References

• Onodera, Shoko et al. "Gorlin Syndrome: Recent Advances in Genetic Testing and Molecular and Cellular Biological Research." International journal of molecular sciences 21.20 (2020): 7559.
• Szczałuba, Krzysztof et al. "Intracardiac tumor as a rare manifestation of genetic syndromes- presentation of a family with Gorlin syndrome and a literature review." Journal of applied genetics 61,4 (2020): 559-565.