Perlman syndrome, an uncommon genetic disorder, is understood to be caused by severe nephrological conditions like nephromegaly, hydronephrosis, nephroblastomatosis, and a strong likelihood of Wilms tumor. Protheragen specializes in preclinical drug and therapy development for Perlman syndrome including the renal aspects of the disorder.
Introduction to Perlman Syndrome
Wilms tumor predisposition and Perlman syndrome is classified as a rare autosomal recessive genetic disorder that presents with distinctive facial features, macrosomia, visceromegaly, hypotonia, and renal anomalies. The incidence of Perlman syndrome and its features is said to exist in every 1 in 1,000,000 births. This is technically the estimated number however the diagnosis rate remains low, which is a possible reason for this number.
Pathogenesis of Perlman Syndrome
Mutations in the DIS3L2 gene, which encodes a cytoplasmic 3'-5' exoribonuclease, is what causes Perlman syndrome. It is responsible for the degradation of certain RNA molecules bearing polyuridylation due to its exoribonuclease activity. A loss of function in the DIS3L2 gene results in incomplete capping of RNA molecules, which during normal cellular operations (such as proliferation, growth, differentiation) will become targets and axiomatic forms of disruption). The combination of internal and external cellular processes, in addition to the renal abnormalities, will progress further in Perlman syndrome cases.
Fig.1 Schematic representation of non-canonical terminal ribonucleotdyl transferases in humans. (Menezes, Balzeau and Hagan, 2018)
Therapeutic Development for Perlman Syndrome
| Drug/Technology |
Therapeutic Target |
Key Findings/Mechanism |
Development Stage |
| Everolimus |
mTOR pathway |
Inhibits hyperactivated mTORC1 signaling |
Phase II trial |
| Interferon β-HSA Fusion Protein |
Immune modulation |
Extended half-life IFNβ with antitumor activity |
Preclinical |
| Bestatin (Ubenimex) |
Aminopeptidase N (APN/CD13) |
Modulates tumor microenvironment and angiogenesis |
Phase I/II trial |
| Lenvatinib |
VEGFR/FGFR/RET pathways |
Multikinase inhibitor targeting tumor angiogenesis |
Phase II trial |
| Vorinostat |
HDAC |
Epigenetic restoration of imprinted gene expression |
Preclinical |
| Dichloroacetate |
Pyruvate dehydrogenase kinase |
Reverses Warburg effect in tumor metabolism |
Preclinical research |
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 specializes in developing advanced
disease models for Perlman syndrome and offers comprehensive
therapeutic development services. We focus on understanding the impact of DIS3L2 deficiency on cellular RNA metabolism, growth pathways, and kidney development.
Therapeutic Development Platform for Perlman Syndrome
Protheragen combines deep expertise in rare genetic disorders, particularly those affecting renal development, with advanced molecular and cellular technologies to address DIS3L2-linked mechanisms in Perlman syndrome.
Disease Models Development for Perlman Syndrome
Protheragen offers innovative and comprehensive
disease models to advance the preclinical research of Perlman syndrome. Our platform integrates
cell-based models,
kidney organoids, and
animal models to capture the genetic and developmental signatures of Perlman syndrome, focusing on renal pathology and supporting extensive drug discovery and mechanism-based investigations.
Cell-based & Organoid Models
- Patient-Derived iPSCs
- DIS3L2-KO HEK293 Cells
- Conditional DIS3L2-KO HK-2 Cells
- iPSC-Derived Kidney Organoids
- Metanephric Mesenchyme-Co-Culture Systems
Animal Models Development
- DIS3L2-/- Knockout Mice
- Six2-Cre; DIS3L2fl/fl Mice
- dis3l2E689K Zebrafish
- DIS3L2-KO Rats with Wilms Tumor Xenografts
- Conditional Dis3l2 Knockout Rats
Protheragen provides integrated preclinical development solutions specifically designed for research in rare genetic kidney diseases like Perlman syndrome. We specialize in
disease model development,
pharmacokinetics, and
drug safety evaluation, enabling us to support your investigation from the initial stages to preclinical validation.
If you are interested in our services, please don't hesitate to
contact us.
References
- Al Ghadeer, H. A., et al. "Dis3l2 Gene Mutation Causes the Perlman Syndrome of Overgrowth and Wilms Tumor Susceptibility." Cureus 15.12 (2023): e49777.
- Menezes, M. R., J. Balzeau, and J. P. Hagan. "3' Rna Uridylation in Epitranscriptomics, Gene Regulation, and Disease." Front Mol Biosci 5 (2018): 61.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
