2026-06-14T03:37:42Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/191132024-11-29T17:52:54Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Bär, Christian
author
Povedano, Juan Manuel
author
Serrano, Rosa
author
Benitez-Buelga, Carlos
author
Popkes, Miriam
author
Formentini, Ivan
author
Bobadilla, Maria
author
Bosch, Fatima
author
Blasco, MA
funder
Ministerio de Economía e Innovación (España)
funder
Roche
funder
Fundacion Botin
2024-04-04T09:35:24Z
2024-04-04T09:35:24Z
2016-04-07
Blood . 2016 ;127(14):1770-9
10.1182/blood-2015-08-667485
1528-0020
Blood
26903545
http://hdl.handle.net/20.500.12105/19113
Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres.
eng
Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.
journal article
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URL
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telomerasegenetherapy_2016.pdf
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text/plain
telomerasegenetherapy_2016.pdf.txt