Simpson-Golabi-Behmel Syndrome (SGBS) is an uncommon X-linked genetic disorder associated with prenatal and postnatal macrosomia, distinct facial features, skeletal anomalies as well as a marked predisposition for some tumors. Protheragen provides a full-range of preclinical drug and therapy development services that aim to explain the SGBS pathophysiology and focus on its renal features and tumor predisposition.
Introduction to Simpson-Golabi-Behmel Syndrome
SGBS is an X-linked recessive genetic disorder with a low incidence of occurrence, predominantly affecting males. However, females who are carriers of the genetic mutation may display symptoms of milder form of the disorder. Common symptoms include dramatic increase in weight and height during and after birth (macrosomia), enlarged distal body parts, coarse facial features, polydactyly, vertebral anomalies, and congenital heart disease. Most importantly, SGBS patients usually deal with several renal abnormalities such as hydronephrosis, polycystic change in kidneys, kidney dysplasia, and horseshoe shaped kidney.
Pathogenesis of Simpson-Golabi-Behmel Syndrome
The disease is mainly a result of the loss of function mutations or deletions of the GPC3 (Glypican-3) gene, found on the X chromosome (Xq26). This gene iS GPC3 a heparan sulfate proteoglycan, which is an important part of cell surface and extracellular matrix. GPC3 functions as a negative modulator of multiple signaling pathways, especially growth factor, including the Insulin like Growth Factor (IGF) system and Wnt signaling pathway. The absence of GPC3 protein function leads to increased signaling and activation of these growth-associated pathways. This uncontrolled signaling is responsible for the lack of control observed in overgrowth features, organ enlargement, and cardial malformation including disrupted renal development.
Fig.1 Diagnosis of Simpson-Golabi-Behmel Syndrome Type 1 via Placental Immunohistochemistry and GPC3 Gene Analysis. (Fiandrino
et al., 2022)
Therapeutics Development for Simpson-Golabi-Behmel Syndrome
| Drug/Technology |
Therapeutic Target |
Key Findings/Mechanism |
Development Stage |
| GC33 Humanized mAb |
GPC3 protein epitope |
Inhibits GPC3-Wnt complex formation to reduce tumor proliferation |
Phase I clinical trial |
| Everolimus |
mTORC1 pathway |
Suppresses PI3K-AKT-mTOR hyperactivation in GPC3 deficiency |
Phase II trial design |
| Recombinant FGF-1 |
Wnt/β-catenin signaling |
Reduces abnormal adipogenesis via β-catenin inhibition |
Preclinical validation |
| Xentuzumab (IGF-II mAb) |
IGF-II/IGF1R axis |
Neutralizes elevated IGF-II to mitigate overgrowth |
Phase II trial |
| Glasdegib |
Hedgehog pathway (SMO receptor) |
Corrects skeletal abnormalities in GPC3 deficiency |
Orphan drug exploration |
| LGK974 (PORCN Inhibitor) |
Wnt ligand secretion |
Blocks GPC3-Wnt-driven tumorigenesis |
Phase I/II trial |
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 is a comprehensive preclinical service provider dedicated to the discovery and development of novel therapeutics for Simpson-Golabi-Behmel syndrome. Our extensive therapeutic development services incorporate the use of sophisticated disease models that effectively capture important features of this inherited overgrowth disorder, with particular emphasis on its renal manifestations and tumor predisposition.
Therapeutic Development Platforms for Simpson-Golabi-Behmel Syndrome
Disease Models Development for Simpson-Golabi-Behmel Syndrome
Protheragen offers innovative and comprehensive disease models to advance preclinical research into SGBS. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the genetic and developmental signatures of SGBS.
- GPC3-KO Human Renal Progenitors
- GPC4 p.R343W Mutant HEK293 Cells
- IGF-2 Overexpressing HK-2 Cells
- Vascular-Kidney Co-Culture System
- Hemizygous Gpc3 Knockout Mice
- Conditional GPC4 Knockout Mice
- Zebrafish with gpc3 Missense Mutation
- IGF-2 mAb-Treated SGBS Rats
Protheragen's integrated preclinical development solutions are specifically designed for research in rare genetic overgrowth syndromes affecting renal and other systems, such as Simpson-Golabi-Behmel syndrome. We specialize in disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation from target validation to IND-enabling studies.
Contact us today to accelerate your Simpson-Golabi-Behmel syndrome research with end-to-end solutions.
References
- Fiandrino, G., et al. "Simpson-Golabi-Behmel Syndrome Type 1: How Placental Immunohistochemistry Can Rapidly Predict the Diagnosis." Placenta 126 (2022): 119-24.
- Guo, Y., et al. "Simpson-Golabi-Behmel Syndrome in One of the Dichorionic-Diamniotic Twin: A Case Report and Literature Review." BMC Pregnancy Childbirth 22.1 (2022): 42.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
