Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare genetic disease defined by low sodium levels in the blood. As a focused research service provider, Protheragen specializes in offering comprehensive, end-to-end solutions for NSIAD and other rare kidney diseases in the scope of drug discovery and development. Our primary aim is to shorten the distance from research to application by offering tailored solutions and state-of-the-art technologies, driving innovation for NSIAD and enabling biopharmaceutical companies and researchers to explore effective therapies for the disorder.
Overview of Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD)
First described in 2005, nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare genetic disorder characterized by hyponatremia, euvolemia, inappropriately concentrated urine, increased natriuresis, and undetectable to very low circulating levels of arginine-vasopressin (AVP). It can present in neonates and infants, or later in life. Early recognition and therapy of NSIAD is crucial to prevent dangerously low levels of hyponatremia, which can severely impact neonatal outcomes, and in fact, potentially leads to death or neurologic sequelae if one survives.
Fig.1 Diagram of AVPR2 mutations causing NSIAD. (Venneri, M.,
et al., 2024)
Pathogenesis of Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD)
Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is an uncommon X-linked recessive genetic disorder characterized by hyponatremia (low sodium) due to an increase in sodium tubular water resorption secondary to activation of arginine vasopressin receptor 2 (AVPR2). Individuals with this disorder have concentrated urine excretion at very low plasma AVP levels, which would otherwise lead to hyponatremia with normal volume (euvolemic hyponatremia). More recently, NSIAD's dominantly inherited features were linked with germline gain-of-function variants in the G protein α-subunit.
Fig.2 Renal cell vasopressin signaling in NSIAD. (Venneri, M.,
et al., 2024)
Therapeutics Development for Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD)
| Therapeutics |
Targets |
Key Findings/Mechanism |
Research Stage |
| Furosemide |
NKCC2 |
A loop diuretic that causes greater excretion of water by inhibiting the tubular reabsorption of sodium and chloride. |
Approved |
| Satavaptan |
AVPR2 |
Selective AVPR2 antagonist; designed to inhibit the overactivation of the mutated receptor responsible for the disease. |
Phase III |
| Tolvaptan |
AVPR2 |
Selective AVPR2 antagonist; inhibits the reabsorption of water through aquaporin-2 channels. |
Approved |
| Sodium chloride |
Salt supplement |
Treats hyponatremia by increasing sodium concentration in the plasma. |
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 offers a complete range of services that will assist you throughout the journey of drug development. We focus on all the aspects of rare diseases from early-phase discovery through to preclinical safety evaluations. We provide such services as preclinical pharmacokinetics, which evaluate the absorption and metabolism of the drugs and the safety evaluation of the drugs to make sure that your therapeutic candidates are safe and effective, as well as therapeutics and diagnostics, and disease model development services.
Therapeutic Development Platforms for NSIAD
Disease Models Development for NSIAD
Accurate disease models play an integral role in the research and development of NSIAD. Among the models we have created and developed, which replicate the salient features of the disease, are cell-based models and organoid models of the kidney, alongside appropriate animal models that allow for rigorous testing and validation of the drugs.
- AVPR2-mutant HEK293T cells
- Patient-derived renal cells
- Induced pluripotent stem cells (iPSCs)
- iPSC-derived kidney organoids
- And more
The animal model for NSIAD consists of genetically engineering an animal, most often a mouse, to possess a gain-of-function mutation in the AVPR2 gene, thereby replicating the human disease.
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
Protheragen's expertise in our rare kidney disease specialization, which, teamed with advanced tech and a dedicated scientific team, makes us the ideal partner for NSIAD therapy research. We ensure comprehensive support and bespoke solutions to meet the unique challenges of drug development and shortened timelines. Looking to advance NSIAD research? Contact us today to discuss how our tailored services can meet your objectives.
References
- Bardanzellu, Flaminia et al. "Focus on neonatal and infantile onset of nephrogenic syndrome of inappropriate antidiuresis: 12 years later." Pediatric nephrology (Berlin, Germany) 34.5 (2019): 763-775.
- Venneri, Maria et al. "Novel signalling pathways in nephrogenic syndrome of inappropriate antidiuresis: functional implication of site-specific AQP2 phosphorylation." The Journal of Physiology 602.13 (2024): 3169-3189.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
