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

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.

Isoenzima de fosfatasa alcalina placental-like, importancia clínica como marcador en tumores de tipo germinal / Clinical relevance of placental-like alkaline phosphatase isoenzyme as a germ cell tumour marker

Fundamento y objetivo. Justificar la importancia clínica de la determinación del isoenzima de fosfatasa alcalina (PLAP-like) como marcador en tumores de células germinales (TCG). Pacientes y métodos. Se documentan dos casos clínicos observando el comportamiento de este isoenzima: 1) Niño con germinoma intracraneal en región pineal, 75% de actividad de PLAP-like al inicio (valor normal: 0%), resto de marcadores tumorales negativos, y 2) Niña con teratoma inmaduro de ovario estadio I, elevación de la alfafetoproteína (AFP), 197ng/mL; PLAP-like 5,1% al inicio y 0,7% en recidiva tumoral tras dos años. Se determina PLAP-like valorando la actividad remanente tras termodesnaturalización sérica. Discusión y conclusiones. PLAP-like se comporta como único marcador específico en el primer caso de tumor germinal pineal que justifica su utilidad junto a pruebas de imagen en el diagnóstico de tumores de localización craneal. En el seguimiento, también es crítico el análisis dado que constata la buena respuesta al tratamiento en el primer caso, y en el segundo caso clínico, es el único marcador que complemente la valoración de la recidiva. Concluimos en la relevancia del análisis de este isoenzima como marcador complementario en TCG (AU)

Background and purpose. To determine the clinical relevance of placental-like alkaline phosphatase isoenzyme (PLAP-like) as a marker for germ cell tumours (GCT). Patients and methods. We report the behaviour of this isoenzyme in two patients; 1) A Child with an intracranial germinoma in the pineal region who showed 75% of PLAP-like activity at onset (normal value: 0%), with the rest of the tumour markers being negative, and 2) A girl with a stage I ovarian immature teratoma who had an elevated alpha-fetoprotein (AFP), 197ng/mL, PLAP-like 5.1%, at onset and 0.7% at tumour recurrence two years later. PLAP-like was determined by assessing the remaining activity after heat denaturation of the serum. Discussion and conclusions. PLAP-like constituted the only specific marker in the case of the pineal cell germ tumour, which justifies its use in association with neuroimaging studies in the diagnosis of cranial tumours. At follow-up analysis, PLAP-like was also critical since it confirmed the good response to treatment in the first case, while in the second one, it was the only marker to complement the assessment of tumour recurrence. We believe that this isoenzyme analysis is of relevance as a complementary marker in GCT (AU)

Enfermedad ósea de Paget asintomática en adulto joven / Asymptomatic Paget´s bone disease in the young adult

Presentamos el caso clínico de un varón de 39 años, diagnosticado de enfermedad ósea de Paget, con afectación ósea craneal y aumento de fosfatasa alcalina sérica e isoenzima ósea. Se realiza revisión de las escasas publicaciones de la enfermedad de Paget en el adulto joven y se sugiere la necesidad de seguir clínicamente cohortes de pacientes con edad de inicio inferior a 40 años(AU)

We discussed the case of a 39 years old man, diagnosed with Paget´s bone disease, with cranial bone affection and raised levels in serum alkaline phosphatase and their bone isoenzyme. We present a review of a few published cases about Paget´s bone disease in early adult life and we suggest to need follow-up cohorts of Paget´s bone disease with early adult onset lower than 40 years(AU)

Biocompatibilidad de los adhesivos dentinarios / Biocompatibility of the dentin adhesives

Se describe el proceso de aislamiento y posterior cultivo de los odontoblastos humanos, identificándolos por sus características fenotípicas y funcionales, una vez identificados se procede la congelación de los mismos en nitrógeno líquido. Se preparan unos discos de cristal sobre los que se pincelan tres adhesivos dentinarios sobre los que se vierte una suspensión de odontoblastos en el medio de cultivo apropiado y se procede a su cultivo. Se estudian las características funcionales de las células en cuanto a síntesis de DNA, actividad de la fosfatasa alcalina, síntesis de colágeno y formación de matriz (AU)

This is a description of the isolation and cultivation of human odontoblasts, and their identification via phenotypic and functional characteristics. Once they have been identified they are frozen in liquid nitrogen. Glass discs are then prepared and three dentin adhesives are applied with a brush, and then a suspension of odontoblasts in a suitable cultivation is poured on and the culture is prepared. The functional characteristics of the cells are studied in terms of DNA synthesis, alkaline phosphate activity, collagen synthesis and matrix formation (AU)