Fibrodysplasia Ossificans Progressiva

The rare genetic disorder Fibrodysplasia ossificans progressiva (FOP) causes muscles and connective tissue to convert into bone which limits movement. Protheragen leads scientific research collaborations to discover new insights and develop innovative therapies for patients affected by this condition.

Characteristics of Fibrodysplasia Ossificans Progressiva

FOP represents a rare genetic disorder where skeletal muscles along with connective tissues including tendons and ligaments undergo progressive ossification. Abnormal bone develops outside the normal skeletal system which leads to restricted movement over time. The initial symptoms appear during early childhood starting at the neck and shoulders before they spread throughout the body. The presence of abnormal big toes at birth serves as a key diagnostic indicator for FOP patients. Trauma or illness can trigger flare-ups that cause muscle swelling and inflammation which leads to permanent bone formation. ACVR1 gene mutations cause this disorder which exhibits autosomal dominant inheritance.

Advancements in Diagnosis and Treatment

Diagnostics Progress

Genetic Diagnosis: Early FOP diagnosis requires genetic testing to identify the ACVR1 gene mutation.
Imaging Techniques: The diagnosis relies on X-rays, CT scans, and MRI scans which help identify abnormal bone growths.
Clinical Manifestations: Children who are developing FOP show early signs through calcification in their feet and hands while their gait becomes abnormal and joints become stiff.

Treatment Advances

Anti-inflammatory Drugs: Doctors use NSAIDs and corticosteroids to reduce inflammation and pain.
BMP Inhibitors: Researchers are conducting clinical trials on BMP pathway inhibitors such as saracitinib because this pathway plays a critical role in FOP.
Immunosuppressants: Current studies investigate how immunosuppressive drugs might help manage FOP symptoms.

(A) Initial steps leading to induction of heterotopic ossification (HO) including injury/infection and inflammatory infiltrate. (B)Schematic shows the initial chondrogenic and cartilage maturation phases of HO tissue development in FOP and known major regulators.

Fig. 1 (A) Initial steps leading to induction of heterotopic ossification (HO) including injury/infection and inflammatory infiltrate. (B)Schematic shows the initial chondrogenic and cartilage maturation phases of HO tissue development in FOP and known major regulators. (Hsiao EC, et al., 2024)

Our Services

Diagnostic Method Development Services for FOP

Genetic Testing: Focuses on detecting ACVR1 gene mutations, particularly R206H, ensuring accurate FOP diagnosis and aiding personalized treatment.
Imaging Techniques: Employ WBCT, MRI, and X-rays to assess heterotopic ossifications' extent and activity.
Biomarker Testing: Use alkaline phosphatase levels for additional diagnostic insights.
Advanced Algorithms: Enhance accuracy with Bayesian algorithms that analyze symptoms and calculate FOP likelihood.

Therapy Development Services for FOP

Drug Development: Target ACVR1/ALK2 and BMP signaling pathways through clinical trials.
Gene Therapy: Use CRISPR to correct ACVR1 mutations, disrupting aberrant pathways.
Innovative Approaches: Explore novel inhibitors and stem cell therapies.

Model Development Services for FOP

In Vitro Models

iPSCs: Derived from FOP patients to study bone disease mechanisms.
Cell Culture: Uses 2D, 3D, and co-culture to investigate FOP-related processes.
Tissue Engineering: Replicates bone and cartilage mineralization.

In Vivo Models:

Transgenic Mouse Models: Mimic FOP traits to explore genetic therapies.
Gene-Edited Mouse Models: Test gene therapy corrections for FOP.
Cell Transplantation Models: Simulate mineralization using patient-derived cells.
Drug Screening Models: Test therapies targeting mineralization inhibition.

The mission of Protheragen focuses on driving innovation and scientific research for FOP. Reach out to us now to discover how our services can promote your research endeavors and drive significant progress in FOP.

Reference

Hsiao EC, Pacifici M. Palovarotene (Sohonos), a synthetic retinoid for reducing new heterotopic ossification in fibrodysplasia ossificans progressiva: history, present, and future. JBMR Plus. 2024 Nov 19;9(1):ziae147.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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