title: Recombinant Enzyme Replacement Therapy in Hypophosphatasia.
abstract: Hypophosphatasia (HPP) is a rare monogenetic and multisystemic disease with involvement of different organs, including bone, muscle, kidney, lung, gastrointestinal tract and the nervous system. The exact metabolic mechanisms of the effects of TNAP deficiency in different tissues are not understood in detail. There is no approved specific treatment for HPP; therefore symptomatic treatment in order to improve the clinical features is of major interest. Enzyme replacement therapy (ERT) is a relatively new type of treatment based on the principle of administering a medical treatment replacing a defective or absent enzyme. Recently ERT with a bone targeted recombinant human TNAP molecule has been reported to be efficient in ten severely affected patients and improved survival of life threatening forms. These results are very promising especially with regard to the skeletal phenotype but it is unclear whether ERT also has beneficial effects for craniosynostosis and in other affected tissues in HPP such as brain and kidney. Long-term data are not yet available and further systematic clinical trials are needed. It is also necessary to establish therapeutic approaches to help patients who are affected by less severe forms of HPP but also suffer from a significant reduction in quality of life. Further basic research on TNAP function and role in different tissues and on its physiological substrates is critical to gain a better insight in the pathogenesis in HPP. This and further experiences in new therapeutic strategies may improve the prognosis and quality of life of patients with all forms of HPP.
authors.affiliation: Children's Hospital, University of Würzburg, Josef-Schneider-Str. 2, 97090, Würzburg, Germany, hofmann_c5@klinik.uni-wuerzburg.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Hofmann
authors.forename: Franz
authors.initials: F
authors.lastname: Jakob
authors.forename: Lothar
authors.initials: L
authors.lastname: Seefried
authors.forename: Birgit
authors.initials: B
authors.lastname: Mentrup
authors.forename: Stephanie
authors.initials: S
authors.lastname: Graser
authors.forename: Horacio
authors.initials: H
authors.lastname: Plotkin
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Girschick
authors.forename: Johannes
authors.initials: J
authors.lastname: Liese
mesh_terms: D000469:Alkaline Phosphatase / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D002352:Carrier Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D056947:Enzyme Replacement Therapy / Q000379:methods; D006801:Humans; D007014:Hypophosphatasia / Q000188:drug therapy*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use*
chemical_list: D002352:Carrier Proteins; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C548267:ALPL protein, human; D000469:Alkaline Phosphatase; C570710:asfotase alfa