Williams Syndrome

Williams syndrome (also referred to as Williams-Beuren syndrome) is a distinctive multisystem disorder. Cardiovascular lesions, due to elastin deficiency, are the major cause of morbidity and mortality associated with Williams syndrome. Protheragen is one of the leading preclinical research service providers in the world committed to the study and therapy of rare diseases such as Williams syndrome. We are also very much committed to delivering one-stop drug discovery and development solutions collaborating with innovators and researchers to turn the rare disease fields into new therapy areas.

Introduction to Williams Syndrome

Williams syndrome is an uncommon microdeletion disorder with an incidence in up to 1:7,500 people. It is a congenital multisystem disease of the cardiovascular, central nervous, and musculoskeletal systems. Cardiovascular abnormalities are present in 80% of individuals and involve arterial stenoses causing the most significant early morbidity and mortality in this condition. The stenoses observed in Williams syndrome can therefore be explained by an insufficient circumferential growth of the arteries.

Fig.1 Multimodality imaging of individuals with supravalvular aortic stenosis. (Micari, A., et al., 2024)

Pathogenesis of Williams Syndrome

Williams syndrome is caused by the misalignment of low-copy DNA repeat elements during meiosis. Deletion size is similar in the majority of these individuals with Williams syndrome with one copy of 25-27 genes on 7q11.23 being deleted. The link between genotype and phenotype is most robust for the elastin (ELN) gene, which is relevant to the archetypical vascular and connective tissue features of Williams syndrome, and for the genes that code for the transcription factors GTF2I and GTF2IRD1, which affect intellectual ability, social behavior, and anxiety. Loss of function of BAZ1B, LIMK1, STX1A, and MLXIPL is also increasingly implicated in various phenotypic presentations.

Fig.2 Phenotypic effects of deletion key genes in the Williams syndrome critical region. (Kozel, B. A., et al., 2021)

Therapeutics Development for Williams 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

With our experience and novel approaches, we also aim to support pioneering research and enhance our comprehension and therapy of Williams syndrome. With expertise and one-stop services in diagnostics, therapeutics, and the development of advanced disease models, we offer the support you need to bring your research to the cutting edge of scientific excellence.

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 Williams Syndrome

Precise animal models need to be created, which are important to identifying its pathogenesis. State-of-the-art, custom Williams syndrome animal model development services for your research needs will be provided by our experienced team of scientists, who will help you through the most suitable strategy in generating a model of the Williams syndrome pathology.

Genetically Engineered Models

Animal models of Williams syndrome are developed that replicate key genetic alterations, which are utilized to mimic neurodevelopmental and cardiovascular aspects of the syndrome.

Optional models:

• Eln knockout model
• Baz1b knockout model

• Complete deletion (CD) mouse model
• Other models

Protheragen's core capabilities with extensive preclinical services, such as pharmacokinetic and drug safety work, make certain every drug candidate meets the safety and efficacy standards needed to proceed to next-stage development. With our unparalleled knowledge and service capabilities, we are uniquely positioned to lead a new era of innovation in rare cardiovascular diseases. Please drop us a contact message if you are interested in our services.

References

• Micari, Antonino et al. "Advanced Multimodality Cardiovascular Imaging of Supravalvular Aortic Stenosis in Williams-Beuren Syndrome." Circulation. Cardiovascular imaging 17.11 (2024): e016733.
• Kozel, Beth A et al. "Williams syndrome." Nature reviews. Disease primers 7.1 (2021): 42.