PMID- 33970241
OWN - NLM
STAT- MEDLINE
DCOM- 20220225
LR  - 20220225
IS  - 1754-8411 (Electronic)
IS  - 1754-8403 (Print)
IS  - 1754-8403 (Linking)
VI  - 14
IP  - 5
DP  - 2021 May 1
TI  - Autosomal recessive osteopetrosis: mechanisms and treatments.
LID - 10.1242/dmm.048940 [doi]
LID - dmm048940
AB  - 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.
CI  - (c) 2021. Published by The Company of Biologists Ltd.
FAU - Penna, Sara
AU  - Penna S
AUID- ORCID: 0000-0002-5036-3809
AD  - San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele 
      Scientific Institute, Milan 20132, Italy.
AD  - Translational and Molecular Medicine (DIMET), University of Milano-Bicocca, Monza 
      20900, Italy.
FAU - Villa, Anna
AU  - Villa A
AUID- ORCID: 0000-0003-4428-9013
AD  - San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele 
      Scientific Institute, Milan 20132, Italy.
AD  - Institute of Genetic and Biomedical Research, Milan Unit, National Research 
      Council, Milan 20090, Italy.
FAU - Capo, Valentina
AU  - Capo V
AUID- ORCID: 0000-0002-1851-1429
AD  - San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele 
      Scientific Institute, Milan 20132, Italy.
AD  - Institute of Genetic and Biomedical Research, Milan Unit, National Research 
      Council, Milan 20090, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210510
PL  - England
TA  - Dis Model Mech
JT  - Disease models & mechanisms
JID - 101483332
SB  - IM
MH  - Consensus
MH  - Gene Expression Regulation
MH  - Genes, Recessive
MH  - Humans
MH  - Osteoclasts/metabolism/pathology
MH  - Osteopetrosis/*genetics/pathology/*therapy
MH  - Practice Guidelines as Topic
PMC - PMC8188884
OTO - NOTNLM
OT  - Bone disease
OT  - Gene therapy
OT  - Hematopoietic stem cell transplantation
OT  - Osteoclast
OT  - Osteopetrosis
COIS- Competing interests The authors declare no competing or financial interests.
EDAT- 2021/05/11 06:00
MHDA- 2022/02/26 06:00
PMCR- 2021/05/10
CRDT- 2021/05/10 12:27
PHST- 2021/05/10 12:27 [entrez]
PHST- 2021/05/11 06:00 [pubmed]
PHST- 2022/02/26 06:00 [medline]
PHST- 2021/05/10 00:00 [pmc-release]
AID - 261835 [pii]
AID - DMM048940 [pii]
AID - 10.1242/dmm.048940 [doi]
PST - ppublish
SO  - Dis Model Mech. 2021 May 1;14(5):dmm048940. doi: 10.1242/dmm.048940. Epub 2021 
      May 10.