Progressive Osseous Heteroplasia (POH)
Progressive osseous heteroplasia (POH) is a rare genetic disorder with an extremely low prevalence rate that leads to progressive bone development in soft tissues. Our company stands at the forefront of rare disease research and offers a spectrum of specialized services ranging from mechanistic investigations to the development of potential therapeutics.
Overview of POH
With an incredibly low prevalence rate, POH is considered a subtype of inactivating PTH / PTHrP signaling disorders (iPPSDs), resulting from heterozygous inactivating mutations of the GNAS gene. The alpha subunit of the G-stimulatory protein of adenylyl cyclase (Gsα) is encoded by the GNAS gene, and mutations in this gene instigate the pathological bone formation seen in POH. Typically, onset in infancy or early childhood, POH progresses gradually throughout an individual's life.
Fig.1 The radiographic image of the foot for POH individuals. (Ma, J., et al., 2023)Pathogenesis of POH
POH is inherited in an autosomal dominant manner and is associated with a mutation of the GNAS gene. Mutation leads to subcutaneous and deep connective tissue ossification that progresses over time. The bone formation usually begins at the surface of the body, such as the skin, and moves into the deeper tissues and muscles. Eventually, the condition may restrict joint movement and impede normal growth and development.
Fig.2 GNAS mutations in individuals with POH. (Ma, J., et al., 2023)Diagnostics Development of POH
Diagnosis of POH primarily relies on the presentation of symptoms observed in individuals, coupled with genetic testing to identify mutations in the GNAS gene that confirm the condition. Various imaging modalities such as X-rays, bone scans, CT scans, and MRI may also bolster the diagnostic process.
Therapeutics of POH
Small Molecule Drugs Therapy
Hedgehog signaling peptide inhibitors can inhibit heterotopic ossification by inhibiting the activation of hedgehog signaling. In addition, retinoic acid receptor γ can reduce the effect of GNAS inactivation by regulating Gsα expression.
Gene Therapy
Gene therapy such as gene editing or RNAi can correct specific mutations of the GNAS gene or specific signaling pathway activation associated with POH, thereby achieving the purpose of inhibiting heterotopic ossification.
Our Services
Our company is at the forefront of the field of rare disease diagnostics and therapeutics research, providing you with animal models and therapeutic development platforms to help you better understand the cause of the disease, identify biomarkers, and create therapeutics.
Platforms of POH Therapy Development
Animal Models of POH
Animal models serve as indispensable tools for studying disease progression and testing novel interventions. We can provide various animal models to help you study the pathogenesis and progression of POH, and ultimately advance your understanding of POH pathophysiology to facilitate the development of effective therapies.
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| Bone morphogenetic proteins (BMPs) are signaling molecules that play a critical role in bone formation and regeneration. Administration of exogenous BMPs, such as BMP-2 or BMP-7, can induce heterotopic ossification in various animal models. | ||
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| Genetically Engineered Models | ||
| Through cutting-edge technologies like CRISPR/cas9 to produce animal models harboring mutations in the GNAS gene—reproducing the genetic alterations seen in human POH individuals. | ||
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| Optional Species | Mice, Rats, Zebrafish, Non-Human Primates, Others | |
Our company brings together scientific expertise, technological advancements, and entrepreneurial spirit to drive innovation and improve human health. We provide comprehensive services related to POH diseases including pharmacokinetics analysis and drug safety evaluation. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Ma, Jing et al. "Progressive osseous heteroplasia in a 5-year-old boy with a novel mutation in exon 2 of GNAS: a case presentation and literature review." BMC musculoskeletal disorders 24.1 (2023): 247.
- Yang, Wan et al. "GNAS locus: bone related diseases and mouse models." Frontiers in endocrinology 14 (2023): 1255864.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.