{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:10:45Z","timestamp":1791389445826,"version":"4.3.3"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"676","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,12,21]]},"abstract":"<jats:p>\n                    Patients with single large-scale mitochondrial DNA (mtDNA) deletion syndromes (SLSMDs) usually present with multisystemic disease, either as Pearson syndrome in early childhood or as Kearns-Sayre syndrome later in life. No disease-modifying therapies exist for SLSMDs. We have developed a method to enrich hematopoietic cells with exogenous mitochondria, and we treated six patients with SLSMDs through a compassionate use program. Autologous CD34\n                    <jats:sup>+<\/jats:sup>\n                    hematopoietic cells were augmented with maternally derived healthy mitochondria, a technology termed mitochondrial augmentation therapy (MAT). All patients had substantial multisystemic disease involvement at baseline, including neurologic, endocrine, or renal impairment. We first assessed safety, finding that the procedure was well tolerated and that all study-related severe adverse events were either leukapheresis-related or related to the baseline disorder. After MAT, heteroplasmy decreased in the peripheral blood in four of the six patients. An increase in mtDNA content of peripheral blood cells was measured in all six patients 6 to 12 months after MAT as compared baseline. We noted some clinical improvement in aerobic function, measured in patients 2 and 3 by sit-to-stand or 6-min walk testing, and an increase in the body weight of five of the six patients suffering from very low body weight before treatment. Quality-of-life measurements as per caregiver assessment and physical examination showed improvement in some parameters. Together, this work lays the ground for clinical trials of MAT for the treatment of patients with mtDNA disorders.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.abo3724","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T13:58:21Z","timestamp":1671631101000},"source":"Crossref","is-referenced-by-count":80,"title":["Mitochondrial augmentation of hematopoietic stem cells in children with single large-scale mitochondrial DNA deletion syndromes"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1411-8942","authenticated-orcid":true,"given":"Elad","family":"Jacoby","sequence":"first","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7052-5238","authenticated-orcid":true,"given":"Omer","family":"Bar-Yosef","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2474-3250","authenticated-orcid":true,"given":"Noah","family":"Gruber","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einat","family":"Lahav","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nira","family":"Varda-Bloom","sequence":"additional","affiliation":[{"name":"Stem Cell Processing Laboratory, Sheba Medical Center, Tel Hashomer 5262000, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2056-8790","authenticated-orcid":true,"given":"Yoav","family":"Bolkier","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9204-3857","authenticated-orcid":true,"given":"Diana","family":"Bar","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moriya Ben-Yakir","family":"Blumkin","sequence":"additional","affiliation":[{"name":"Minovia Therapeutics, Tirat HaCarmel 3902603, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0714-4798","authenticated-orcid":true,"given":"Sharon","family":"Barak","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Department of Nursing, Faculty of Health Sciences, Ariel University, Ariel 40700, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6323-2533","authenticated-orcid":true,"given":"Etzyona","family":"Eisenstein","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9353-2684","authenticated-orcid":true,"given":"Jaana","family":"Ahonniska-Assa","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"School of Behavioral Sciences, Academic College of Tel Aviv Yaffo, Tel Aviv 64044, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Silberg","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Department of Psychology, Bar-Ilan University, Ramat-Gan 52900, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4691-6797","authenticated-orcid":true,"given":"Tal","family":"Krasovsky","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Department of Physical Therapy, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa 34988, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Bar","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neta","family":"Erez","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bella","family":"Bielorai","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Golan","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Dekel","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9233-0458","authenticated-orcid":true,"given":"Michal J.","family":"Besser","sequence":"additional","affiliation":[{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel."},{"name":"Ella Lemelbaum Institute of Immuno-oncology, Sheba Medical Center, Tel Hashomer 5262000, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0452-9043","authenticated-orcid":true,"given":"Gat","family":"Pozner","sequence":"additional","affiliation":[{"name":"Minovia Therapeutics, Tirat HaCarmel 3902603, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4690-5003","authenticated-orcid":true,"given":"Hanan","family":"Khoury","sequence":"additional","affiliation":[{"name":"Minovia Therapeutics, Tirat HaCarmel 3902603, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7211-7334","authenticated-orcid":true,"given":"Alan","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Minovia Therapeutics, Tirat HaCarmel 3902603, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Campbell","sequence":"additional","affiliation":[{"name":"Minovia Therapeutics, Tirat HaCarmel 3902603, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Herskovitz","sequence":"additional","affiliation":[{"name":"Minovia Therapeutics, Tirat HaCarmel 3902603, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noa","family":"Sher","sequence":"additional","affiliation":[{"name":"Minovia Therapeutics, Tirat HaCarmel 3902603, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-7441","authenticated-orcid":true,"given":"Natalie","family":"Yivgi-Ohana","sequence":"additional","affiliation":[{"name":"Minovia Therapeutics, Tirat HaCarmel 3902603, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Anikster","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amos","family":"Toren","sequence":"additional","affiliation":[{"name":"Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer 5262000, Israel."},{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/331717a0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-015-7710-y"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114881"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9778-4"},{"key":"e_1_3_3_6_2","first-page":"37","volume-title":"JIMD Reports","author":"Farruggia P.","year":"2016","unstructured":"P. Farruggia, A. Di Cataldo, R. M. Pinto, E. Palmisani, A. Macaluso, L. Lo Valvo, M. E. Cantarini, A. Tornesello, P. Corti, F. Fioredda, S. Varotto, B. Martire, I. Moroni, G. Puccio, G. Russo, C. Dufour, M. Pillon, Giuseppe Puccio, Giovanna Russo, Carlo Dufour, Marta Pillon: Pearson Syndrome: A Retrospective Cohort Study from the Marrow Failure Study Group of A.I.E.O.P. (Associazione Italiana Emato-Oncologia Pediatrica), in JIMD Reports, 26E. Morava, M. Baumgartner, M. Patterson, S. Rahman, J. Zschocke, V. PetersEds.Springer2016374310.1007\/978-3-662-49833-0."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2018.1426454"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt321"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0221829"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61433"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1038\/gim.2017.107","article-title":"Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society","volume":"19","author":"Parikh S.","year":"2017","unstructured":"S. Parikh, A. Goldstein, A. Karaa, M. K. Koenig, I. Anselm, C. Brunel-Guitton, J. Christodoulou, B. H. Cohen, D. Dimmock, G. M. Enns, M. J. Falk, A. Feigenbaum, R. E. Frye, J. Ganesh, D. Griesemer, R. Haas, R. Horvath, M. Korson, M. C. Kruer, M. Mancuso, S. McCormack, M. J. Raboisson, T. Reimschisel, R. Salvarinova, R. P. Saneto, F. Scaglia, J. Shoffner, P. W. Stacpoole, C. M. Sue, M. Tarnopolsky, C. Van Karnebeek, L. A. Wolfe, Z. Zolkipli Cunningham, S. Rahman, P. F. Chinnery, Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet. Med. 19, 1380\u20131397 (2017). 10.1038\/gim.2017.107.","journal-title":"Genet. Med."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510511103"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90423-0"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-021-00167-7"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2736"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaj2347"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-08-2597"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032613"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv226"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708262"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30220"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-9948-7"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2006.08.006"},{"key":"e_1_3_3_24_2","doi-asserted-by":"crossref","unstructured":"S.\u00a0M.\u00a0Haley W.\u00a0Coster L.\u00a0H.\u00a0Ludlow J.\u00a0T.\u00a0Haltiwanger P.\u00a0J.\u00a0Andrellos Pediatric Evaluation of Disability Inventory (PEDI) (1992).","DOI":"10.1037\/t08316-000"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/aos.14095"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001265"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aav9824"},{"key":"e_1_3_3_28_2","first-page":"334","article-title":"Alteration in the copy number of mitochondrial DNA in leukocytes of patients with mitochondrial encephalomyopathies","volume":"113","author":"Liu C. S.","year":"2006","unstructured":"C. S.\u00a0Liu, W. L.\u00a0Cheng, C. F.\u00a0Lee, Y. S.\u00a0Ma, C. Y.\u00a0Lin, C. C.\u00a0Huang, Y. H.\u00a0Wei,Alteration in the copy number of mitochondrial DNA in leukocytes of patients with mitochondrial encephalomyopathies. Acta Neurol. Scand.113,334\u2013341 (2006).","journal-title":"Acta Neurol. Scand."},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1159\/000229763"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000214966.60416.1b"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17434"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-545830"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1705638"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21615"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0550-z"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.04.039"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.abo3724","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T12:58:45Z","timestamp":1705409925000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.abo3724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,21]]},"references-count":35,"journal-issue":{"issue":"676","published-print":{"date-parts":[[2022,12,21]]}},"alternative-id":["10.1126\/scitranslmed.abo3724"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.abo3724","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,21]]},"article-number":"eabo3724"}}