Hypophosphataemic rickets is a genetic condition that leads to rickets due to improper renal handling of phosphorus. Its presentation is seen in infancy or early childhood as skeletal deformities and growth plate changes. Here at Protheragen, we are focused on the research of rare kidney diseases to help accelerate drug development. We provide full support in drug development for hypophosphataemic rickets, including foundational research, preclinical studies, and all other steps in the comprehensive drug development pipeline.
Overview of Hypophosphataemic Rickets
Hypophosphataemic rickets refers to a diverse set of conditions marked by rickets or osteomalacia resulting from inadequate phosphate, stemming primarily from decreased renal reabsorption. Additionally, they have defective absorption of calcium from the intestine, rickets or osteomalacia unresponsive to cholecalciferol, and other metabolic abnormalities. Consequently, there is stunted growth, bone pain, other deformities, and dwarfism. There are two classifications of hypophosphataemic rickets.
- Individuals having mutations in extrarenal factors will have excess fibroblast growth factor 23 (FGF23) levels.
- Individuals with normal or low FGF23 levels have mutations in renal tubular phosphate transporters.
Fig.1 Daily phosphate transport. (Ito, N.,
et al., 2024)
Pathogenesis of Hypophosphataemic Rickets
Hypophosphataemic rickets is a rare disorder that arises from severe phosphate wasting in the kidneys, which may involve the factor FGF23 prominently. The more common ones are genetic, like in X-linked hypophosphataemic rickets, where it is caused by unregulated FGF23 resulting from a mutation in the PHEX gene. This mutation is responsible for the hypophosphataemic rickets, causing diminished tubular phosphate reabsorption, reduced renal 1α-hydroxylase activity, and increased renal 24-hydroxylase activity.
Fig.2 FGF23/PTH regulation of proximal tubule phosphate transport. (Ito, N.,
et al., 2024)
Therapeutics Development for Hypophosphataemic Rickets
| Therapeutics |
Targets |
Key Findings/Mechanism |
Research Stage |
| Burosumab |
FGF23 |
Monoclonal antibody therapy to mitigate FGF23 results in boosting renal reabsorption of phosphate along with the production of calcitriol. |
Approved |
| Calcitriol |
/ |
The oral supplements aim to replace lost phosphate and improve the intestinal absorption of both phosphate and calcium. |
Approved |
| Alfacalcidol |
/ |
Corrects hypophosphatemia and the lowered concentration of 1,25(OH)2D. |
Approved |
| INZ-701 |
ENPP1 |
An ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement therapy. |
Phase II |
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 both the research and drug development of hypophosphataemic rickets, offering a one-stop shop solution. Our services encompass the entire continuum of drug discovery, including diagnostics and therapeutics, as well as the development of disease models. Our preclinical studies also include assessing the pharmacokinetics and safety of the drug, ensuring it is both safe and effective. We enhance research efficiency by integrating services and thus reducing the time to commercialization.
Therapeutic Development Platforms for Hypophosphataemic Rickets
Disease Models Development for Hypophosphataemic Rickets
Disease models are vital for grasping the pathophysiology of hypophosphataemic rickets and for evaluating the efficacy and safety of new pharmaceutical candidates. We focus on developing and employing validated cellular models, kidney organoids, and animal models that faithfully replicate the human condition. We have the ability to offer these models, which ensures efficient conducting of your preclinical studies.
Cell-based & Organoid Models
- SaOS-2 cells with FGF23 overexpression
- Opossum kidney (OK) cells
- PHEX-KO human iPSCs
- iPSC-derived kidney organoids
- And more
Animal Models
- Hyp mouse model
- Dmp1 knockout model
- Enpp1 knockout model
- FGF23 transgenic 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
Here at Protheragen, we aim to be your reliable collaborator in combating hypophosphataemic rickets. Some of our advantages are profound scientific knowledge in the area of rare kidney diseases, a broad range of services, as well as an emphasis on enhancing your research schedule. Reach out to us today to learn how we can assist you in moving your promising drug candidates from the envision to the preclinical phase.
References
- Yamazaki, Miwa, and Toshimi Michigami. "Osteocytes and the pathogenesis of hypophosphatemic rickets." Frontiers in endocrinology 13 (2022): 1005189.
- Ito, Nobuaki et al. "The pathophysiology of hypophosphatemia." Best practice & research. Clinical endocrinology & metabolism 38.2 (2024): 101851.
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only and cannot be used to diagnose, treat or manage patients.
