Marfan Syndrome

Marfan syndrome, a systemic disorder of connective tissues, has life-threatening complications related to the cardiovascular system, such as mitral valve prolapse, aortic insufficiency, aortic root dilatation, and aortic dissection. Dedicated to the therapy development for rare cardiovascular diseases such as Marfan syndrome, Protheragen is a leading preclinical research service provider that has the most extensive and complete drug discovery and development powers.

Introduction to Marfan Syndrome

Marfan syndrome is a systemic disorder of connective tissue, with an incidence from 1.5 to 17.2 in every 100,000 population, and the phenotype is predominantly based on cardiovascular, ocular, and skeletal involvement. Aortal involvement and its complications in Marfan syndrome including thoracic/abdominal aortic aneurysm, aortal dissection, and acute aortic syndrome. Dissecting thoracic aortic aneurysm and advancing dilation of the aortic root represent the primary sources of morbidity and mortality in Marfan syndrome.

Fig.1 Potential biomarkers for Marfan syndrome. (Stengl, R., et al., 2021)

Pathogenesis of Marfan Syndrome

Marfan syndrome is usually inherited as an autosomal dominant trait, due to heterozygous mutations in FBN1. The FBN1 gene codes for the fibrillin-1 protein, a critical constituent of the ECM. It plays a structural and regulatory role. Fibrillin-1, due to its structural role, is incorporated in the ECM as a member of the microfibrils. Mutations in fibrillin-1 not only lead to the loosing of the ECM structure but will also likely affect the control of the cytokine TGFβ. In Marfan syndrome aortic tissues, the TGFβ signaling pathway is over-active, which will lead to changes in the expression of its target genes such as CTGF and MMPs.

Fig.2 TGF signaling in Marfan syndrome. (Du, Q., et al., 2021)

Therapeutics Development for Marfan Syndrome

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

Using state-of-the-art technology and a wealth of experience, we work to streamline the end-to-end process from discovery to application, helping you develop new therapies faster. Our efforts in the area of diagnostic development employ the most current techniques to ascertain and interpret disease markers, and therapeutic research addresses novel approaches directed at the rare diseases themselves. Additionally, we provide advanced disease model engineering, in vitro and in vivo models, for proof-of-concept models.

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 Marfan Syndrome

Animal models of Marfan syndrome are key to the development of new research tools and new potential therapies for this rare cardiovascular disease. Acknowledging the importance of animal models, our company offers customized animal model development services specifically focusing on Marfan syndrome. By providing accurate and consistent models, we enable researchers to undertake potent preclinical studies.

Genetically Engineering Animal Model

Genetically modified animal models for Marfan syndrome in which specific mutations are introduced into the FBN1 gene to mimic the features of the disease.

Optional models:

• Fbn1^mgΔ/mgΔ
• Fbn1^mgR/mgR
• Fbn1^C1039G/+

• Fbn1^C1041G/+
• Other models

Protheragen's team is passionate about driving innovation. We work closely with partners on their path to developing therapies for rare cardiovascular diseases. Additionally, our integrated preclinical services include pharmacokinetic studies and drug safety testing, necessary to help establish a drug's safety and to avoid development delays. Contact us now to find out how we can help with your R&D.

References

• Stengl, Roland et al. "Potential predictors of severe cardiovascular involvement in Marfan syndrome: the emphasized role of genotype-phenotype correlations in improving risk stratification-a literature review." Orphanet journal of rare diseases 16.1 (2021): 245.
• Du, Qiu et al. "The Molecular Genetics of Marfan Syndrome." International journal of medical sciences 18.13 (2021): 2752-2766.