Liddle syndrome is a rare form of hypertension that is passed down genetically as an autosomal dominant condition. It is characterized by an increase in sodium reabsorption and secretion of potassium in the kidney tubules. As a foremost provider of research services for rare kidney diseases, Protheragen offers a comprehensive range of services for research and drug development for Liddle syndrome.
Overview of Liddle Syndrome
Liddle syndrome is one of the uncommon causes of difficult-to-treat high blood pressure, which can present as early as childhood. This syndrome is uncommon, resulting from a genetic change involving the collecting tubule sodium channel that alters its function, which causes hypertension. In this genetic disorder, the hallmark signs are high blood pressure, low potassium levels, and metabolic alkalosis. From a pathological point of view, the levels of renin and aldosterone are both suppressed.
Fig.1 Structure of ENaC. (Enslow, B. T.,
et al., 2019)
Pathogenesis of Liddle Syndrome
Liddle syndrome is a hereditary type of hypertension with a dominant pattern of inheritance. Mutation within the ENaC genes leads to increased activity of the distal nephron's epithelial sodium channel, which alters sodium transport. Epithelial sodium channels (ENaC) are made up of 3 homologous subunits, the ENaC's alpha, beta, and gamma subunits, which are coded by SCNN1A, SCNN1B, and SCNN1G genes. The resulting mutation causes hypertension as a consequence of increased sodium ion reabsorption and expansion of volume.
Fig.2 Phenotype-genotype correlations in Liddle syndrome. (Granhøj, J.,
et al., 2024)
Therapeutics Development for Liddle Syndrome
| Therapeutics |
Targets |
Key Findings/Mechanism |
Research Stage |
| Triamterene |
ENaC |
Inhibits the absorption of sodium in the distal convoluted tubule. |
Approved |
| Amiloride |
ENaC |
Blocks the distal convoluted tubule sodium channels. |
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's platform supports every aspect of your drug development process from discovery to preclinical verification. We also offer advanced disease model development in diagnostics and therapeutics. Our preclinical research services also encompass pharmacokinetic and toxicology studies, along with biosafety evaluation, ensuring that all regulatory and safety requirements are met for your drug candidate.
Therapeutic Development Platforms for Liddle Syndrome
Disease Models Development for Liddle Syndrome
Supported by extensive genetic and physiological research, Protheragen is able to develop and characterize robust disease models that accurately replicate human Liddle syndrome pathology. Such models are essential for comprehending the progression of the disease as well as for preclinical trials of innovative therapeutic modalities. We provide several of these models, including cellular models and more complex models, such as relevant animal models and kidney organoids. Each is tailored to specific research requirements.
- Primary cell model
- Patient-derived kidney organoids
- iPSC-derived kidney organoids
- And more
- SCNN1B CKO animal model
- SCNN1G CKO animal model
- SCNN1A CKO animal model
- And more
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
In Vivo Pharmacokinetics
- PK Studies in Renal Impairment Models
- Kidney Tissue Distribution Study
- Blood-to-Plasma Ratio
- Metabolite Profiling
With an intricate understanding of rare renal disorders, Protheragen is an ideal partner to collaborate on your Liddle syndrome research. We leverage advanced tools along with tailored service for the expedited progress of your drug discovery endeavors. Our staff is devoted to resolving the obstacles associated with the therapy of rare diseases, providing targeted, high-caliber solutions crafted for your needs. Reach out to us today to find out more about how our specialized services can propel your research forward.
References
- Granhøj, Jeff et al. "Reverse Phenotypes of Patients with Genetically Confirmed Liddle Syndrome." Clinical journal of the American Society of Nephrology: CJASN 19.5 (2024): 610-619.
- Enslow, Benjamin T et al. "Liddle's syndrome mechanisms, diagnosis and management." Integrated blood pressure control 12 (2019): 13-22.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
