Gordon Syndrome (GS), also known as Pseudohypoaldosteronism type 2 (PHA2), is a rare genetic disorder characterized by hypertension, hyperkalemia, and metabolic acidosis. Protheragen provides drug and therapeutic development services for rare kidney diseases, including Gordon syndrome.
Introduction to Gordon Syndrome
Gordon Syndrome, or Pseudohypoaldosteronism Type 2 (PHA2), is a rare, autosomal dominant genetic disorder characterized by a unique combination of hypertension, hyperkalemia, and metabolic acidosis. These symptoms occur despite normal or low renin and aldosterone levels, which is distinct from other forms of salt-sensitive hypertension. The condition is caused by a dysregulation of salt reabsorption in the kidney, specifically within the distal convoluted tubule and collecting duct. The disease is inherited in an autosomal dominant manner, with an estimated prevalence of 1 in 1,000,000 individuals worldwide.
Pathogenesis of Gordon Syndrome
Fig.1 Schematic representation of the WNK1 gene and protein. (Noris, Daina and Remuzzi, 2023)
Gordon Syndrome is primarily driven by mutations in the WNK1 gene, which encodes WNK1 kinase, a protein that regulates ion transport in the renal distal convoluted tubule. Mutations in WNK1 lead to dysregulation of sodium, chloride, and potassium transporters, particularly the Na-Cl co-transporter (NCC), which becomes overactive. This results in salt retention, hyperkalemia, and metabolic acidosis, which can ultimately contribute to the development of hypertension. The disease pathophysiology is often linked to an impaired response of the kidneys to aldosterone, which further exacerbates the abnormal electrolyte imbalances. The activation of the WNK signaling pathway increases the activity of other kinases such as SPAK and OSR1, further disrupting sodium and potassium homeostasis.
Therapeutic Development for Gordon Syndrome
| Drug Name |
Target |
Key Mechanism & Findings |
Current Stage |
| Amiloride |
Epithelial sodium channel (ENaC) |
Reduces potassium excretion, useful in managing hyperkalemia in GS patients |
Approved |
| Spironolactone |
Mineralocorticoid receptor |
Blocks aldosterone effects, helps in managing hypertension and hyperkalemia in GS |
Approved |
| Espironolactone |
Mineralocorticoid receptor |
Similar to spironolactone, used to manage electrolyte imbalances and hypertension |
Approved |
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 Gordon syndrome and offers comprehensive preclinical therapeutic development. We focus on understanding the diverse genetic impacts that lead to the renal salt dysregulation characteristic of this condition.
Therapeutic Development Platform for Gordon Syndroem
Protheragen combines deep expertise in renal physiology, ion transport biology, and the genetics of kidney disorders with advanced molecular and cellular technologies to address the multifaceted mechanisms leading to Gordon syndrome.
Disease Models Development for Gordon Syndrome
Protheragen offers a comprehensive range of advanced disease models to support preclinical research into Gordon syndrome. Our disease models capture the genetic and physiological aspects of GS, enabling researchers to explore the molecular and cellular mechanisms of this disorder and develop effective therapies.
Cell-based & Organoid Models
- WNK1 Knockout Human Renal Cells
- iPSC-Derived Renal Tubuloid Models for GS
- Human Podocytes with WNK1 Mutations
- Human Mesangial Cells
Animal Models Development
- WNK1 Knockout Mouse Model
- Gordon Syndrome Rat Model
- Zebrafish WNK1 Knockout Model
- Transgenic Mice with WNK1 Mutations
Drug Pharmacokinetics & Safety Evaluation Services
In Vitro ADME Services
- Renal Clearance Assay
- Drug-Transporter Interaction Screening
- Metabolic Stability Assay
- CYP Inhibition Screening
- Plasma Protein Binding
Protheragen is committed to advancing the understanding and treatment of Gordon syndrome. Through our integrated preclinical development solutions, including disease model development, pharmacokinetics, and drug safety evaluation we are dedicated to accelerating the development of effective therapies for this rare and challenging condition.
If you are interested in our services, please don't hesitate to contact us.
References
- Noris, M., E. Daina, and G. Remuzzi. "Gordon Syndrome: No Longer the Same Disease and May Need Very Different Treatment." Nephrol Dial Transplant 38.2 (2023): 283-90.
- Yu, S. M., et al. "Gordon Syndrome Pattern of Injury." Adv Kidney Dis Health 31.3 (2024): 216-22.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
