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Recombinant Enzyme Replacement Therapy in Hypophosphatasia

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Neuronal Tissue-Nonspecific Alkaline Phosphatase (TNAP)

Part of the book series: Subcellular Biochemistry ((SCBI,volume 76))

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.

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Conflict of Interest

JL and CH received a study grant from Enobia and Alexion Pharma (Cheshire, Connecticut, U.S.) for a phase two study on Asfotase alpha treatment for severe forms of HPP. F. Jakob has received honoraria and travel support for lectures and advice from Eli Lilly, Amgen, Novartis, MSD, Nycomed, Servier, Roche, Enobia and Alexion Pharma, he has received unrestricted research grants from Novartis and is involved in clinical studies related to osteoporosis drugs initiated by Eli Lilly, Amgen, Servier and Novartis. HG served on an advisory board of Enobia/Alexion. HP was a full-time employee of Alexion 2012–1013.

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Authors and Affiliations

  1. Children’s Hospital, University of Würzburg, Josef-Schneider-Str. 2, 97090, Würzburg, Germany

    Christine Hofmann & Johannes Liese

  2. Orthopedic Department, Orthopedic Center for Musculoskeletal Research, University of Würzburg, Würzburg, Germany

    Franz Jakob, Lothar Seefried, Birgit Mentrup & Stephanie Graser

  3. Children’s Hospital, Vivantes Hospital im Friedrichshain, Berlin, Germany

    Hermann J. Girschick

  4. University of Nebraska Medical Center, Omaha, NE, USA

    Horacio Plotkin

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  1. Christine Hofmann
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  2. Franz Jakob
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  3. Lothar Seefried
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  4. Birgit Mentrup
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  5. Stephanie Graser
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  8. Johannes Liese
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Correspondence to Christine Hofmann .

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Editors and Affiliations

  1. National Centre for Scientific Research (CNRS), University of Toulouse-UPS, Toulouse, France

    Caroline Fonta

  2. Wigner Research Centre for Physics, Hungarian Academy of Sciences, Budapest, Hungary

    László Négyessy

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Hofmann, C. et al. (2015). Recombinant Enzyme Replacement Therapy in Hypophosphatasia. In: Fonta, C., Négyessy, L. (eds) Neuronal Tissue-Nonspecific Alkaline Phosphatase (TNAP). Subcellular Biochemistry, vol 76. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7197-9_15

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