Pseudohypoaldosteronism Type 1 (PHA1)
Pseudohypoaldosteronism type 1 (PHA1) is a complex and rare heterogeneous syndrome that manifests as a deficiency in transepithelial sodium transport. Our company stands as a leader in innovation in rare diseases like PHA1, offering a myriad of advantages tailored to support researchers and scientists dedicated to unraveling the complexities of these conditions.
Introduction to PHA1
PHA1 is a rare genetic disorder characterized by aldosterone unresponsiveness in the distal nephron. Aldosterone, a pivotal hormone in maintaining salt and water balance in the body, fails to function effectively in individuals with PHA1. As a result, affected individuals experience a range of symptoms, including salt wasting, dehydration, hyperkalemia (high blood potassium levels), and metabolic acidosis.
Fig.1 Distribution of variants by location and type. (Gao, Z., et al., 2023)Pathogenesis of PHA1
PHA1 is categorized based on the underlying genetic background, with distinctions between renal (autosomal dominant) and generalized (autosomal recessive) forms. Renal PHA1 is also known as PHA1A and is associated with mutations in the mineralocorticoid receptor gene (NR3C2). On the other hand, systemic PHA1, referred to as PHA1B, is linked to mutations in the subunits of the epithelial sodium channel (ENaC) - namely, SCNN1A, SCNN1B, and SCNN1G.
Fig.2 Simplified scheme of ENaC regulation and targets for ENaC modulation. (Lemmens-Gruber, R., and Tzotzos, S., 2023)
Diagnostics Development of PHA1
Biochemical Testing
Biochemical tests focusing on electrolyte levels and hormone evaluations are instrumental in managing PHA1, including measuring electrolyte levels (sodium, potassium, chloride, and bicarbonate) and assessing aldosterone and renin levels.
Genetic Testing
Genetic testing plays a crucial role in confirming a diagnosis of PHA1. Testing typically involves sequencing the genes associated with aldosterone resistance, such as NR3C2 for PHA1A and SCNN1A, SCNN1B, and SCNN1G for PHA1B.
Therapeutics Development of PHA1
| Types | Drug Names | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|---|
| Small molecule drug | Kayexalate | An orally active plasma potassium inhibitor | Potassium | Approved |
| Synthetic Peptides | Solnatide | Restoration of ENaC function | ENaC | Phase II trials |
| Synthetic Peptides | AP318 | Restore ENaC function | ENaC | Clinical research |
Our Services
With our company's animal model and therapeutic development platform, we can ensure that researchers have all the essential support and expertise they require to advance their work effectively. We aim to empower you to push the boundaries of knowledge, gain novel insights into rare diseases like PHA1, and drive progress toward improved diagnostics and therapeutics.
Therapeutics Development Platforms
Animal Models of PHA1
Animal models play a crucial role in unraveling the intricacies of PHA1 and testing potential therapy strategies. Our company provides a diverse range of animal models that mimic aspects of aldosterone resistance and related electrolyte imbalances, enabling researchers to gain deeper insights into the pathophysiology of this rare genetic disorder.
| Genetically Engineered Models | ||
| Genetic engineering animal models are modified to carry mutations in genes that are associated with PHA1 in humans, such as the genes encoding for the mineralocorticoid receptor or the ENaC. | ||
| Optional Models |
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| Optional Species | Mice, Rats, Non-Human Primates, Others | |
Why Choose Us
Our company specializes in rare diseases and provides a comprehensive suite of services tailored to the unique requirements of PHA1 research. From pharmacokinetic studies to drug safety evaluations, our services are designed to support researchers in their quest to advance knowledge and develop novel therapeutic approaches for PHA1.
If you are interested in our service, we invite you to contact us for further information and to obtain detailed quotations.
References
- Gao, Zhen et al. "Pseudohypoaldosteronism type 1b in fraternal twins of a Chinese family: report of two cases and literature review." Archives of endocrinology and metabolism 67.4 (2023): e000620.
- Lemmens-Gruber, Rosa, and Susan Tzotzos. "The Epithelial Sodium Channel-An Underestimated Drug Target." International journal of molecular sciences 24.9 (2023): 7775.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.