HDR syndrome is a rare genetic disorder characterized by a constellation of developmental defects including Hypoparathyroidism, Sensorineural Deafness, and Renal abnormalities, often due to mutations in the GATA3 gene. Protheragen provides comprehensive preclinical drug and therapy development services tailored to address the unique mechanisms of HDR syndrome, with a focus on renal-related therapeutic strategies.
Overview of HDR Syndrome
This syndrome is an autosomal dominant disease associated with the haploinsufficiency of the GATA3 gene. It is estimated that only a few hundred cases have been reported throughout the world, which makes this syndrome rare. Regardless of expressing variability, most cases have incomplete penetrance. A key feature of this syndrome, the renal component, is commonly observed as kidney dysplasia, hypoplasia, or sometimes even aplasia. In addition to these, some patients can also suffer from cystic kidneys, pelvicalyceal deformities, or vesicoureteral reflux, which often leads to chronic kidney disease.
Pathogenesis of HDR Syndrome
The HDR syndrome is caused by a combination of genetic factors including heterozygous loss-of-function mutations or deletions of the GATA3 gene. GATA3 is a crucial transcription factor that impacts many developmental programs within the cells, including growth, survival, and differentiation of the organs. Functional GATA3 protein, when reduced, fails to support the protective and restorative processes in significant developmental programs. In the kidney, GATA3 is needed for the orderly branching morphogenesis of the ureteric bud as well as for other renal cell types including mesangial cells. Its lack leads to the dysgenic kidney which is unable to form sufficient functioning nephrons.
Fig.1 Three-dimensional structure of the GATA3. (Huang
et al., 2024)
Therapeutics Development for HDR Syndrome
| Drug/Technology |
Therapeutic Target |
Key Mechanism |
Development Stage |
| NU7441 + Ribociclib |
NHEJ/HDR pathway modulation |
DNA-PK inhibition with CDK4/6 inhibition |
Preclinical |
| AAV9-GATA3 gene therapy |
GATA3 haploinsufficiency |
AAV9-mediated gene replacement |
Preclinical |
| Eteplirsen-like antisense oligonucleotide |
GATA3 splicing defects |
Exon skipping to restore splicing |
Preclinical |
| Recombinant PTH |
Hypocalcemia management |
PTH replacement therapy |
Approved (off-label use) |
| CaSR antagonists (e.g., Etelcalcetide) |
Hypocalcemia symptoms |
Calcium homeostasis regulation |
Phase III clinical 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 provider of preclinical research services aimed at the therapeutic development of HDR Syndrome. We employ disease models that recapitulate the triad of hypoparathyroidism, sensorineural deafness, and renal dysplasia for mechanism-based drug discovery for this rare monogenic disorder.
Therapeutic Development Platforms for HDR Syndrome
Disease Models Development for HDR Syndrome
Protheragen provides specific disease models to accelerate preclinical research on HDR Syndrome. Our platform integrates cell-based models, kidney organoids, and animal models. These models incorporate multi-omics profiling and functional validation to support target identification and therapeutic efficacy testing for HDR-specific pathways.
Cell-based & Organoid Models
- Patient-derived iPSCs
- GATA3 mutant cell lines
- GATA3 knockout HEK293 cell lines
- iPSC-based kidney organoids
- GATA3 mutant kidney organoids
Animal Models
- Gata3+/- heterozygous knockout mice
- Conditional Gata3 knockout mice
- Zebrafish gata3 mutation models
- Chromosome 10p13 deletion models
Protheragen offers end-to-end preclinical development services tailored to HDR Syndrome's unique challenges. 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
- Goncalves, C. I., et al. "Hypoparathyroidism, Deafness and Renal Dysplasia Syndrome Caused by a Gata3 Splice Site Mutation Leading to the Activation of a Cryptic Splice Site." Front Endocrinol (Lausanne) 14 (2023): 1207425.
- Huang, B., et al. "A Novel Gata3 Frameshift Mutation Causes Hypoparathyroidism, Sensorineural Deafness, and Renal Dysplasia Syndrome." Mol Genet Metab Rep 38 (2024): 101063.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
