Novel Therapeutic Agents for Rare Diseases of Calcium and Phosphate Metabolism

Author:

Roumpou Afroditi12ORCID,Yavropoulou Maria P.3,Chronopoulos Efstathios2,Kassi Eva234

Affiliation:

1. Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, “Aghia Sofia” Children’s Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece

2. Laboratory for Research of the Musculoskeletal System, National and Kapodistrian University of Athens School of Medicine, Athens, Greece

3. Centre of Expertise for Rare Endocrine Diseases, C.E.R.E.D. Disorders of Calcium & Phosphate Metabolism, First Department of Propaedeutic and Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece

4. Department of Biological Chemistry, National and Kapodistrian University of Athens, Athens, Greece

Abstract

AbstractThe last decade has been revolutionary regarding the management of rare bone diseases caused by impaired calcium and phosphate metabolism. Elucidation of the underlying genetic basis and pathophysiologic alterations has been the determinant factor for the development of new, disease-specific treatment agents. The phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) possesses a critical role in the pathogenesis of various hypophosphatemic disorders. Among them, the genetic disorder of X-linked hypophosphatemia and the acquired syndrome of tumor-induced osteomalacia, although very rare, have attracted the scientific community’s attention towards designing an FGF23-inhibitor as a potential specific therapy. The monoclonal antibody burosumab was approved for the treatment of children and adult patients with X-linked hypophosphatemia and recently for tumor-induced osteomalacia patients, demonstrating benefits regarding their symptoms, biochemical profile and bone mineralization status. Asfotase alfa is a hydroxyapatite-targeted recombinant alkaline phosphatase, an enzymatic replacement therapy, substituting the defective activity of tissue non-specific alkaline phosphatase, in patients suffering from hypophosphatasia. Promising data regarding its favorable effect on survival rate, bone quality, fracture healing, muscle strength, mobility, respiratory function, and general quality of life have led to the approval of the drug for the treatment of childhood-onset hypophosphatasia. Given the high costs of treatment for both agents and their limited clinical use until now, more data are needed to define patients’ characteristics that make them ideal candidates for therapy. Long-term safety issues also need to be clarified.

Publisher

Georg Thieme Verlag KG

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,General Medicine,Endocrinology, Diabetes and Metabolism

Reference79 articles.

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2. FGF23-related hypophosphatemic rickets/osteomalacia: diagnosis and new treatment;S Fukumoto;J Mol Endocrinol,2021

3. The measurement and interpretation of fibroblast growth factor 23 (FGF23) concentrations;A C Heijboer;Calcif Tissue Int,2022

4. New therapies for hypophosphatemia-related to FGF23 Excess;D Athonvarangkul;Calcif Tissue Int,2021

5. Genetic causes of rickets;S Acar;J Clin Res Pediatr Endocrinol,2017

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