Hypophosphatasia
Hypophosphatasia, a rare genetic disorder, impacts bone and teeth health by causing a deficiency in alkaline phosphatase, an essential enzyme in the body. Our company, equipped with extensive experience and expertise in hypophosphatasia research, provides comprehensive services across all stages of investigation.
Overview of Hypophosphatasia
Hypophosphatasia is a rare genetic metabolic disease, the prevalence varies, estimated to affect a range from 1 in 100,000 to 1 in 900,000 live births. It stems from mutations in the ALPL gene, leading to decreased alkaline phosphatase activity, subsequently lowering inorganic phosphate and calcium levels in bones and teeth, resulting in weakened mineralization.
Fig.1 Features of hypophosphatasia in the pediatric and adult individual population with some overlapping features between the two age groups. (Khan, A. A., et al., 2024)Pathogenesis of Hypophosphatasia
The pathogenesis of hypophosphatasia involves mutations in the ALPL gene, reducing the activity of tissue non-specific alkaline phosphatase (TNAP). This decrease causes a buildup of substrates such as inorganic pyrophosphate (PPi) and pyridoxal-5'-phosphate (PLP). The accumulation of these substances contributes to the musculoskeletal and systemic manifestations seen in the disease.
Fig.2 Mechanisms of mineralisation involving TNAP. (Salles J. P., 2020)Diagnostics Development of Hypophosphatasia
A genetic diagnosis, crucial for hypophosphatasia detection, involves identifying ALPL or other genes that regulate TNAP activity (such as RUNX2) mutations through methods like serial single-gene testing or a multigene panel strategy.
Therapeutics of Hypophosphatasia
Conventional Therapy
Enzyme Replacement Therapy
Gene Therapy
Our Services
Our company offers comprehensive services encompassing animal model construction and therapeutic platform development to support your research to better understand and develop innovative therapies for hypophosphatasia.
Platforms of Hypophosphatasia Therapy Development
Animal Models of Hypophosphatasia
Animal models provide valuable insights into the pathophysiology of hypophosphatasia and help in the development of potential therapeutics for this rare genetic disorder. We can provide chemical induction and genetic engineering animal models to help you delve deep into the pathogenesis and develop innovative therapies.
| Chemical-induced Models | ||
| Chemical-induced animal models of hypophosphatasia involve the administration of compounds, such as levamisole, that inhibit TNAP activity and lead to a phenotype mimicking the disease of hypophosphatasia. | ||
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| Genetically Engineered Models | ||
| Genetic engineering animal models using transgenic or gene editing techniques such as CRISPR/Cas9 leads to changes in the expression of related genes. These models exhibit similar skeletal and dental abnormalities as seen in human individuals with the disease. | ||
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| Optional Species | Mice, Rats, Sheep, Non-Human Primates, Others | |
With cutting-edge technology and a team of skilled professionals, we can support your pharmacokinetics analysis and drug safety evaluation, and committed to advancing research in this rare genetic disorder and providing valuable insights for the development of effective therapeutics.
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Salles, Jean Pierre. "Hypophosphatasia: Biological and Clinical Aspects, Avenues for Therapy." The Clinical biochemist 41.1 (2020): 13-27.
- Khan, Aliya A et al. "Hypophosphatasia diagnosis: current state of the art and proposed diagnostic criteria for children and adults." Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 35.3 (2024): 431-438.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.