Autosomal recessive osteopetrosis: mechanisms and treatments
Autosomal recessive osteopetrosis (ARO) is a severe inherited bone disease characterized by defective osteoclast resorption or differentiation. Clinical manifestations include dense and brittle bones, anemia and progressive nerve compression, which hamper the quality of patients' lives and caus...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2021-05-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/14/5/dmm048940 |
| _version_ | 1819066557459857408 |
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| author | Sara Penna Anna Villa Valentina Capo |
| author_facet | Sara Penna Anna Villa Valentina Capo |
| author_sort | Sara Penna |
| collection | DOAJ |
| description | Autosomal recessive osteopetrosis (ARO) is a severe inherited bone disease characterized by defective osteoclast resorption or differentiation. Clinical manifestations include dense and brittle bones, anemia and progressive nerve compression, which hamper the quality of patients' lives and cause death in the first 10 years of age. This Review describes the pathogenesis of ARO and highlights the strengths and weaknesses of the current standard of care, namely hematopoietic stem cell transplantation (HSCT). Despite an improvement in the overall survival and outcomes of HSCT, transplant-related morbidity and the pre-existence of neurological symptoms significantly limit the success of HSCT, while the availability of human leukocyte antigen (HLA)-matched donors still remains an open issue. Novel therapeutic approaches are needed for ARO patients, especially for those that cannot benefit from HSCT. Here, we review preclinical and proof-of-concept studies, such as gene therapy, systematic administration of deficient protein, in utero HSCT and gene editing. |
| first_indexed | 2024-12-21T16:04:15Z |
| format | Article |
| id | doaj.art-ce42f204027e4fc98e9fae213af25f86 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-21T16:04:15Z |
| publishDate | 2021-05-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-ce42f204027e4fc98e9fae213af25f862022-12-21T18:57:55ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112021-05-0114510.1242/dmm.048940048940Autosomal recessive osteopetrosis: mechanisms and treatmentsSara Penna0Anna Villa1Valentina Capo2 San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan 20132, Italy San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan 20132, Italy San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan 20132, Italy Autosomal recessive osteopetrosis (ARO) is a severe inherited bone disease characterized by defective osteoclast resorption or differentiation. Clinical manifestations include dense and brittle bones, anemia and progressive nerve compression, which hamper the quality of patients' lives and cause death in the first 10 years of age. This Review describes the pathogenesis of ARO and highlights the strengths and weaknesses of the current standard of care, namely hematopoietic stem cell transplantation (HSCT). Despite an improvement in the overall survival and outcomes of HSCT, transplant-related morbidity and the pre-existence of neurological symptoms significantly limit the success of HSCT, while the availability of human leukocyte antigen (HLA)-matched donors still remains an open issue. Novel therapeutic approaches are needed for ARO patients, especially for those that cannot benefit from HSCT. Here, we review preclinical and proof-of-concept studies, such as gene therapy, systematic administration of deficient protein, in utero HSCT and gene editing.http://dmm.biologists.org/content/14/5/dmm048940osteopetrosisbone diseaseosteoclasthematopoietic stem cell transplantationgene therapy |
| spellingShingle | Sara Penna Anna Villa Valentina Capo Autosomal recessive osteopetrosis: mechanisms and treatments Disease Models & Mechanisms osteopetrosis bone disease osteoclast hematopoietic stem cell transplantation gene therapy |
| title | Autosomal recessive osteopetrosis: mechanisms and treatments |
| title_full | Autosomal recessive osteopetrosis: mechanisms and treatments |
| title_fullStr | Autosomal recessive osteopetrosis: mechanisms and treatments |
| title_full_unstemmed | Autosomal recessive osteopetrosis: mechanisms and treatments |
| title_short | Autosomal recessive osteopetrosis: mechanisms and treatments |
| title_sort | autosomal recessive osteopetrosis mechanisms and treatments |
| topic | osteopetrosis bone disease osteoclast hematopoietic stem cell transplantation gene therapy |
| url | http://dmm.biologists.org/content/14/5/dmm048940 |
| work_keys_str_mv | AT sarapenna autosomalrecessiveosteopetrosismechanismsandtreatments AT annavilla autosomalrecessiveosteopetrosismechanismsandtreatments AT valentinacapo autosomalrecessiveosteopetrosismechanismsandtreatments |