Work

Profile of asfotase alfa in the treatment of hypophosphatasia: design, development, and place in therapy

Year: 2018

Type: article

Abstract: : Hypophosphatasia (HPP) is a multi-systemic metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the mineralization-associated enzyme, tissue-nonspecific alkaline phosphatase (TNSALP). HPP is characterized by defective bone and dental mineralization, leading to skeletal abnormalities with complications resulting in significant morbidity and mortality. Management of HPP has been limited to supportive care until the introduction of a recently approved enzyme replacement therapy employing bone-targeted recombinant human TNSALP, asfotase alfa (AA). This new therapy has been transformative as it improves survival in severely affected infants, and overall quality of life in children and adults with HPP. This review provides an overview of HPP, focusing on important steps in the development of AA enzyme replacement therapy, including the drug design, preclinical studies in the HPP mouse model, and outcomes from clinical trials and case report publications to date, with special attention given to response to therapy of skeletal manifestations, biochemical features, and other clinical manifestations. The limitations, adverse effects, and outcomes of AA are outlined and the place in therapy for individuals with HPP is discussed. Keywords: alkaline phosphatase, bone mineralization, rickets, osteomalacia, teeth, enzyme replacement therapy, inorganic pyrophosphate

Source: Drug Design Development and Therapy

DOI: 10.2147/dddt.s154922

Authors: Sasigarn A. Bowden, Brian L. Foster

Institutions: Nationwide Children's Hospital, The Ohio State University

Language: English

Topic: Alkaline Phosphatase Research Studies

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836