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

Bowden, Sasigarn A; Foster, Brian L.

doi:10.2147/dddt.s154922

Cited by 36 publications

(25 citation statements)

References 108 publications

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“…Hypophosphatasia (HPP) is an inherited systemic skeletal disease caused by loss-of-function mutations in Alkaline Phosphatase, Biomineralization associated (ALPL) gene that encodes tissue-nonspecific alkaline phosphatase (TNSALP) (1). Deficient TNSALP activity leads to accumulation of inorganic pyrophosphate, which is the substrate of alkaline phosphatase (ALP) and an inhibitor of hydroxyapatite formation (2), resulting in defective bone and/or teeth mineralization (3).…”

Section: Introductionmentioning

confidence: 99%

Odontohypophosphatasia treated with asfotase alfa enzyme replacement therapy in a toddler: a case report

Takagi

Kato

Muto

et al. 2020

Clin Pediatr Endocrinol

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Hypophosphatasia (HPP) is a rare skeletal disorder caused by loss-of-function mutations in Alkaline Phosphatase, Biomineralization associated (ALPL) gene that encodes tissue-nonspecific alkaline phosphatase. Odontohypophosphatasia (odonto-HPP), a mild form of HPP, is characterized only by oral manifestations including premature exfoliation of deciduous teeth. Enzyme replacement therapy (ERT) is effective in severe HPP cases; however, information about its efficacy for odonto-HPP is limited. A 2-yr-old girl was referred to our hospital for mobility of her deciduous teeth with low serum alkaline phosphatase (ALP) level of 253 U/L (reference range: 410-1,150 U/L) and high urine phosphoethanolamine level of 1,419.9 µmol/g•Cre (7-70 µmol/g•Cre). She had no history of bone fractures; however, several members of her family had low serum ALP levels with a history of pathological fractures. She had a novel heterozygous missense mutation (c.1183A>T, p.Ile395Phe) in ALPL, and therefore, was diagnosed with odonto-HPP. After she was provided ERT to prevent premature exfoliation, no tooth mobility was observed. However, two deciduous teeth exfoliated two months after starting ERT, which was possibly triggered by a bout of common cold. Starting ERT following tooth mobility might be relatively late. Previous studies on experimental mice showed that starting ERT at birth may be effective in preventing premature exfoliation of deciduous teeth.

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Section: Introductionmentioning

confidence: 99%

Odontohypophosphatasia treated with asfotase alfa enzyme replacement therapy in a toddler: a case report

Takagi

Kato

Muto

et al. 2020

Clin Pediatr Endocrinol

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“…PPi is a substrate of TNSALP and an inhibitor of hard tissue mineralisation, sometimes described as the body’s ‘natural water softener’. High levels of PPi (substrate accumulation) block hydroxyapatite crystal growth, resulting in impaired bone or tooth mineralisation and thus rachitic symptoms [69] (Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

“…3HPP mechanism of disease. Image used under the creative commons attribution license 3.0 from Bowden et al [69]…”

Section: Resultsmentioning

confidence: 99%

The evolving therapeutic landscape of genetic skeletal disorders

Sabir

Cole

2019

Orphanet J Rare Dis

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Background: Rare bone diseases account for 5% of all birth defects yet very few have personalised treatments. Developments in genetic diagnosis, molecular techniques and treatment technologies however, are leading to unparalleled therapeutic advance. This review explores the evolving therapeutic landscape of genetic skeletal disorders (GSDs); the key conditions and there key differentials. Methods: A retrospective literature based review was conducted in December 2018 using a systematic search strategy for relevant articles and trials in Pubmed and clinicaltrials.gov respectively. Over 140 articles and 80 trials were generated for review. Results: Over 20 personalised therapies are discussed in addition to several novel disease modifying treatments in over 25 GSDs. Treatments discussed are at different stages from preclinical studies to clinical trials and approved drugs, including; Burosumab for X-linked hypophosphatemia, Palovarotene for Hereditary Multiple Exostoses, Carbamazepine for Metaphyseal Chondrodysplasia (Schmid type), Lithium carbonate and anti-sclerostin therapy for Osteoporosis Pseudoglioma syndrome and novel therapies for Osteopetrosis. We also discuss therapeutic advances in Achondroplasia, Osteogenesis Imperfecta (OI), Hypophosphotasia (HPP), Fibrodysplasia Ossificans Progressiva, and RNA silencing therapies in preclinical studies for OI and HPP. Discussion: It is an exciting time for GSD therapies despite the challenges of drug development in rare diseases. In discussing emerging therapies, we explore novel approaches to drug development from drug repurposing to in-utero stem cell transplants. We highlight the improved understanding of bone pathophysiology, genetic pathways and challenges of developing gene therapies for GSDs.

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“…Эффективность и безопасность использования препарата оценивалась в проспективных открытых многоцентровых клинических исследованиях (NCT00952484, NCT01203826) у больных с перинатальной, инфантильной и детской формами гипофосфатазии [19]. По мере накопления результатов клинических исследований было показано значительное улучшение минерализации, гистологической структуры костной ткани, увеличение общей выживаемости пациентов на фоне лечения асфотазой альфа [19,20]. В настоящее время имеются данные, свидетельствующие об эффективности фермент-заместительной терапии TNSALP у подростков и взрослых пациентов с гипофосфатазией [10,21].…”

Section: Discussionunclassified

Clinical application experience of asfotase alfa for a young patient with childhood hypophosphatasia

Kalinchenko¹,

Golounina²,

Grebennikova³

et al. 2019

Osteopor Bone Dis

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Hypophosphatasia (HPP) is a rare hereditary metabolic disease characterized by defective bone and dental mineralization, systemic complications that lead to disability of patients. HPP is classified into six forms according to the age of onset and severity of its clinical picture. The disease is caused by a reduced activity of the tissue nonspecific alkaline phosphatase (TNSALP) and elevated concentrations of pyrophosphates. Asfotase alfa is the only pathogenetic enzyme replacement therapy with recombinant human bone-targeted TNSALP approved for treatment of patients with perinatal, infantile and juvenile‐onset HPP. This treatment is associated with improved skeletal mineralization, respiratory function and overall survival in infants and young children with life-threatening hypophosphatasia. The world experience in application of recombinant alkaline phosphatase in adults is very limited. We present a clinical case that describes the first Russian experience in the use of asfotase alfa in an 18-year-old patient with late diagnosis of childhood-onset HPP.

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

Cited by 36 publications

References 108 publications

Odontohypophosphatasia treated with asfotase alfa enzyme replacement therapy in a toddler: a case report

Odontohypophosphatasia treated with asfotase alfa enzyme replacement therapy in a toddler: a case report

The evolving therapeutic landscape of genetic skeletal disorders

Clinical application experience of asfotase alfa for a young patient with childhood hypophosphatasia

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