The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy
Open accessAbstract
BACKGROUND: In X-linked adrenoleukodystrophy, mutations in ABCD1 lead to loss of function of the ALD protein. Cerebral adrenoleukodystrophy is characterized by demyelination and neurodegeneration. Disease progression, which leads to loss of neurologic function and death, can be halted only with allogeneic hematopoietic stem-cell transplantation. METHODS: We enrolled boys with cerebral adrenoleukodystrophy in a single-group, open-label, phase 2-3 safety and efficacy study. Patients were required to have early-stage disease and gadolinium enhancement on magnetic resonance imaging (MRI) at screening. The investigational therapy involved infusion of autologous CD34+ cells transduced with the elivaldogene tavalentivec (Lenti-D) lentiviral vector. In this interim analysis, patients were assessed for the occurrence of graft-versus-host disease, death, and major functional disabilities, as well as changes in neurologic function and in the extent of lesions on MRI. The primary end point was being alive and having no major functional disability at 24 months after infusion. RESULTS: A total of 17 boys received Lenti-D gene therapy. At the time of the interim analysis, the median follow-up was 29.4 months (range, 21.6 to 42.0). All the patients had gene-marked cells after engraftment, with no evidence of preferential integration near known oncogenes or clonal outgrowth. Measurable ALD protein was observed in all the patients. No treatment-related death or graft-versus-host disease had been reported; 15 of the 17 patients (88%) were alive and free of major functional disability, with minimal clinical symptoms. One patient, who had had rapid neurologic deterioration, had died from disease progression. Another patient, who had had evidence of disease progression on MRI, had withdrawn from the study to undergo allogeneic stem-cell transplantation and later died from transplantation-related complications. CONCLUSIONS: Early results of this study suggest that Lenti-D gene therapy may be a safe and effective alternative to allogeneic stem-cell transplantation in boys with early-stage cerebral adrenoleukodystrophy. Additional follow-up is needed to fully assess the duration of response and long-term safety. (Funded by Bluebird Bio and others; STARBEAM ClinicalTrials.gov number, NCT01896102 ; ClinicalTrialsRegister.eu number, 2011-001953-10 .).
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The former is associated with its own degree of morbidity and mortality [62], and both require the patient undergo chemotherapy [48].”
From Structure and Function of the ABCD1 Variant Database: 20 Years, 940 Pathogenic Variants, and 3400 Cases of Adrenoleukodystrophy (2022) · cites this paper as [48]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Early-stage treatment of childhood cerebral ALD with hematopoietic stem cell transplantation and, more recently, gene therapy can arrest disease progression if performed in the window of opportunity when the MRI is abnormal but neurological symptoms are not yet apparent [7,38,43,44,45,46,47,48,49,50].”
From Structure and Function of the ABCD1 Variant Database: 20 Years, 940 Pathogenic Variants, and 3400 Cases of Adrenoleukodystrophy (2022) · cites this paper as [48]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, they are useful only as the first signs of abnormalities are noted on magnetic resonance imaging (MRI) of the brain, before the onset of any neurological symptoms.”
From Identification of a Novel Non-Canonical Splice-Site Variant in ABCD1 (2023) · cites this paper as [6]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Thus, prompt diagnosis can improve the prognosis of CALD in boys [2,3,4,5,6].”
From Identification of a Novel Non-Canonical Splice-Site Variant in ABCD1 (2023) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, an autologous hematopoietic stem cell transplantation after ex vivo lentiviral gene therapy has been developed (Eichler et al., 2017).”
From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Eichler et al., 2017
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“This novel variant was classified as a VUS according to the ACMG PM2, PP3, and PP4 criteria [6], and confirmed using Sanger sequencing (Figure 2B).”
From Identification of a Novel Non-Canonical Splice-Site Variant in ABCD1 (2023) · cites this paper as [6]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1
Hacein-Bey-Abina, S., Garrigue, A., Wang, G. P., Soulier, J., Lim, A., Morillon, E., Clappier, E., Caccavelli, L., Delabesse, E., Beldjord, K., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35700 · Cited by 1,854
Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy
Cartier, N., Hacein-Bey-Abina, S., Bartholomae, C. C., Veres, G., Schmidt, M., Kutschera, I., Vidaud, M., Abel, U., Dal-Cortivo, L., Caccavelli, L., et al. (2009) · Science · doi:10.1126/science.1171242 · Cited by 1,508
Self-citationHowe, S. J., Mansour, M. R., Schwarzwaelder, K., Bartholomae, C., Hubank, M., Kempski, H., Brugman, M. H., Pike-Overzet, K., Chatters, S. J., de Ridder, D., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35798 · Cited by 1,286
Self-citationGene therapy returns to centre stage
Naldini, L. (2015) · Nature · doi:10.1038/nature15818 · Cited by 1,184
Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy
Biffi, A., Montini, E., Lorioli, L., Cesani, M., Fumagalli, F., Plati, T., Baldoli, C., Martino, S., Calabria, A., Canale, S., et al. (2013) · Science · doi:10.1126/science.1233158 · Cited by 1,180
Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome
Aiuti, A., Biasco, L., Scaramuzza, S., Ferrua, F., Cicalese, M. P., Baricordi, C., Dionisio, F., Calabria, A., Giannelli, S., Castiello, M. C., et al. (2013) · Science · doi:10.1126/science.1233151 · Cited by 1,025
Stein, S., Ott, M., Schultze‐Strasser, S., Jauch, A. S., Burwinkel, B., Kinner, A., Schmidt, M., Krämer, A., Schwäble, J., Glimm, H., et al. (2010) · Nature Medicine · doi:10.1038/nm.2088 · Cited by 792
Self-citationEngelen, M., Kemp, S., de Visser, M., van Geel, B. M., Wanders, R. J., Aubourg, P., & Poll-The, B. (2012) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-7-51 · Cited by 562
Self-citationAdrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy
Moser, H. (1997) · Brain · doi:10.1093/brain/120.8.1485 · Cited by 478
A Modified γ-Retrovirus Vector for X-Linked Severe Combined Immunodeficiency
Hacein-Bey-Abina, S., Pai, S.-Y., Gaspar, H. B., Armant, M., Berry, C. C., Blanche, S., Bleesing, J., Blondeau, J., de Boer, H., Buckland, K. F., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1404588 · Cited by 412
Self-citation
Research works printed but not linked: 2
- Loes DJ, 1994, AJNR Am J Neuroradiol, 15, 1761
- Amartino H, 2017, J Inborn Errors Metab Screen, 5, 1
Cited by
Sorted by citations
Dunbar, C. E., High, K. A., Joung, J. K., Kohn, D. B., Ozawa, K., & Sadelain, M. (2018) · Science · doi:10.1126/science.aan4672 · Cited by 1,410
Viral vector platforms within the gene therapy landscape
Bulcha, J. T., Wang, Y., Ma, H., Tai, P. W. L., & Gao, G. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00487-6 · Cited by 1,404
Gene therapy clinical trials worldwide to 2012 – an update
Ginn, S. L., Alexander, I. E., Edelstein, M. L., Abedi, M. R., & Wixon, J. (2013) · The Journal of Gene Medicine · doi:10.1002/jgm.2698 · Cited by 1,187
Inflammation in CNS neurodegenerative diseases
Stephenson, J., Nutma, E., van der Valk, P., & Amor, S. (2018) · Immunology · doi:10.1111/imm.12922 · Cited by 966
Gene therapy clinical trials worldwide to 2017: An update
Ginn, S. L., Amaya, A. K., Alexander, I. E., Edelstein, M., & Abedi, M. R. (2018) · The Journal of Gene Medicine · doi:10.1002/jgm.3015 · Cited by 903
Measuring biological aging in humans: a quest
Ferrucci, L., Gonzalez‐Freire, M., Fabbri, E., Simonsick, E., Tanaka, T., Moore, Z., Salimi, S., Sierra, F., & de Cabo, R. (2020) · Aging Cell · doi:10.1111/acel.13080 · Cited by 781
“…with human aging in stem cell numbers, characteristics, and replication potential are still limited (Dexheimer, Mueller, Braatz, & Richter, 2011; Eichler et al., 2017; Fan et al., 2010; Golpanian et al., 2017, 2016; Hare et al., 2012; Jim et al., 2016; Li, Chen, Han, & Fu, 2010; Pang et al.,…”
BackgroundAdvances in Regenerative Medicine and Tissue Engineering: Innovation and Transformation of Medicine
Dzobo, K., Thomford, N. E., Senthebane, D. A., Shipanga, H., Rowe, A., Dandara, C., Pillay, M., & Motaung, K. S. (2018) · Stem Cells International · doi:10.1155/2018/2495848 · Cited by 477
“Most 3D bioprinting processes and stem cell therapies require the use of synthetic and natural biological molecules such as growth factors to enhance the proliferation and differentiation of stem cells [155, 301].”
BackgroundTherapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality
Hudry, E., & Vandenberghe, L. H. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.017 · Cited by 384
Therapies for rare diseases: therapeutic modalities, progress and challenges ahead
Tambuyzer, E., Vandendriessche, B., Austin, C. P., Brooks, P. J., Larsson, K., Miller Needleman, K. I., Valentine, J., Davies, K., Groft, S. C., Preti, R., et al. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0049-9 · Cited by 357
for the European Society for Blood and Marrow Transplantation (EBMT), Duarte, R. F., Labopin, M., Bader, P., Basak, G. W., Bonini, C., Chabannon, C., Corbacioglu, S., Dreger, P., Dufour, C., et al. (2019) · Bone Marrow Transplantation · doi:10.1038/s41409-019-0516-2 · Cited by 354
Gene therapy using haematopoietic stem and progenitor cells
Ferrari, G., Thrasher, A. J., & Aiuti, A. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-00298-5 · Cited by 263
Self-citationHematopoietic Stem Cell Gene Therapy: Progress and Lessons Learned
Morgan, R. A., Gray, D., Lomova, A., & Kohn, D. B. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.10.010 · Cited by 252
“X-Linked Adrenoleukodystrophy HSC Gene Therapy A recent report described efficacious HSC gene therapy for X-linked Adrenoleukodystrophy (X-ALD), a progressive neurodegenerative disorder with onset in boys during the first 1 to 2 decades (Eichler et al., 2017).”
BackgroundThe physiological functions of human peroxisomes
Wanders, R. J. A., Baes, M., Ribeiro, D., Ferdinandusse, S., & Waterham, H. R. (2023) · Physiological Reviews · doi:10.1152/physrev.00051.2021 · Cited by 228
Marktel, S., Scaramuzza, S., Cicalese, M. P., Giglio, F., Galimberti, S., Lidonnici, M. R., Calbi, V., Assanelli, A. A., Bernardo, M. E., Rossi, C., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0301-6 · Cited by 229
Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency
Kohn, D. B., Booth, C., Shaw, K. L., Xu‐Bayford, J., Garabedian, E., Trevisan, V., Carbonaro-Sarracino, D. A., Soni, K., Terrazas, D., Snell, K., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2027675 · Cited by 223
Self-citationTurk, B. R., Theda, C., Fatemi, A. S., & Moser, A. B. (2020) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.10003 · Cited by 212
“correction of CD34-positive stem cells is ongoing(Cartier et al., 2009; Eichler et al., 2017).”
AAV-based in vivo gene therapy for neurological disorders
Ling, Q., Herstine, J. A., Bradbury, A. M., & Gray, S. J. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00766-7 · Cited by 223
Gene therapy targeting haematopoietic stem cells for inherited diseases: progress and challenges
Cavazzana, M., Bushman, F. D., Miccio, A., André‐Schmutz, I., & Six, E. M. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0020-9 · Cited by 205
Biomanufacturing for clinically advanced cell therapies
Aijaz, A., Li, M., Smith, D. W., Khong, D., LeBlon, C. E., Fenton, O. S., Olabisi, R. M., Libutti, S. K., Tischfield, J. A., Maus, M. V., et al. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0246-6 · Cited by 198
Therapeutic strategies for sickle cell disease: towards a multi-agent approach
Telen, M. J., Malik, P., & Vercellotti, G. M. (2018) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0003-2 · Cited by 188
Bak, R. O., Gomez‐Ospina, N., & Porteus, M. H. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.05.004 · Cited by 181
Diagnosis, prognosis, and treatment of leukodystrophies
van der Knaap, M. S., Schiffmann, R., Mochel, F., & Wolf, N. I. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30143-7 · Cited by 175
Rı́o, P., Navarro, S., Wang, W., Sánchez‐Domínguez, R., Pujol, R. M., Segovia, J. C., Bogliolo, M., Merino, E., Wu, N., Salgado, R., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0550-z · Cited by 167
Köhler, W., Curiel, J., & Vanderver, A. L. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.175 · Cited by 158
Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy
Duncan, C., Bledsoe, J. R., Grzywacz, B. J., Beckman, A., Bonner, M. A., Eichler, F., Kühl, J., Harris, M. H., Slauson, S. R., Colvin, R. A., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2405541 · Cited by 161
Self-citationTucci, F., Galimberti, S., Naldini, L., Valsecchi, M. G., & Aiuti, A. (2022) · Nature Communications · doi:10.1038/s41467-022-28762-2 · Cited by 149
Lynch, D. S., Wade, C., de Paiva, A. R. B., John, N. A., Kinsella, J. A., Merwick, Á., Ahmed, R. M., Warren, J. D., Mummery, C. J., Schott, J. M., et al. (2018) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2018-319481 · Cited by 146
Raymond, G. V., Aubourg, P., Paker, A., Escolar, M., Fischer, A., Blanche, S., Baruchel, A., Dalle, J.-H., Michel, G., Prasad, V., et al. (2019) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2018.09.036 · Cited by 142
Self-citationPan, J., Qu, M., Li, Y., Wang, L., Zhang, L., Wang, Y., Tang, Y., Tian, H., Zhang, Z., & Yang, G. (2019) · Stroke · doi:10.1161/strokeaha.119.027531 · Cited by 137
“clinic now, but lentivirus-modified hematopoietic stem cells have been used in clinical trial.(36) Gene therapy is a novel approach to treat ischemic brain injury.”
MethodHuman genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type I
Gomez‐Ospina, N., Scharenberg, S. G., Mostrel, N., Bak, R. O., Mantri, S., Quadros, R. M., Gurumurthy, C. B., Lee, C. M., Bao, G., Suarez, C. J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11962-8 · Cited by 124
Clinical application of next-generation sequencing to the practice of neurology
Rexach, J. E., Lee, H., Martínez-Agosto, J. A., Nemeth, A. H., & Fogel, B. L. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30033-x · Cited by 117
Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app
van Konijnenburg, E. M. M. H., Wortmann, S. B., Koelewijn, M. J., Tseng, L. A., Houben, R. F. A., Stöckler‐Ipsiroglu, S., Ferreira, C. R., & van Karnebeek, C. (2021) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-021-01727-2 · Cited by 121
Immune-evasive gene switch enables regulated delivery of chondroitinase after spinal cord injury
Burnside, E. R., de Winter, F., Didangelos, A., James, N. D., Andreica, E.-C., Horsfall, H. L., Muir, E. M., Verhaagen, J., & Bradbury, E. J. (2018) · Brain · doi:10.1093/brain/awy158 · Cited by 114
“However, recent success with lentiviral-mediated gene therapy for the treatment of cerebral adrenoleukodystrophy in children (Eichler et al., 2017) also highlights the ongoing potential of lentivirus-based systems for clinical use.”
BackgroundGenetic engineering of hematopoiesis: current stage of clinical translation and future perspectives
Naldini, L. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201809958 · Cited by 115
“Today > 200 patients have been treated worldwide by LV-based HSC GT for several diseases, including ALD (Eichler et al, 2017), MLD (Sessa et al, 2016); WAS (Biasco et al, 2016); chronic granulomatous disorder, some PID (De Ravin et al, 2016b); and mucopolysaccharidoses, thalassemia, and sickle cell disease (Cavazzana-…”
BackgroundTepavčević, V., & Lubetzki, C. (2022) · Brain · doi:10.1093/brain/awac307 · Cited by 115
Production of Lentiviral Vectors Using Suspension Cells Grown in Serum-free Media
Bauler, M. N., Roberts, J. K., Wu, C., Fan, B., Ferrara, F., Yip, B. H., Diao, S., Kim, Y., Moore, J., Zhou, S., et al. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.11.011 · Cited by 105
Designing Lentiviral Vectors for Gene Therapy of Genetic Diseases
Poletti, V., & Mavilio, F. (2021) · Viruses · doi:10.3390/v13081526 · Cited by 111
“The only notable exception is the LV developed for gene therapy of adrenoleukodystrophy (ALD), in which a cDNA for the ATP-binding cassette, subfamily D, member 1 (ABCD1) is driven by a modified (MND) MPSV enhancer/promoter [14,17] (Figure 1B, #1).”
BackgroundLoss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy
Pant, D. C., Dorboz, I., Schlüter, A., Fourcade, S., Launay, N., Joya, J., Aguilera, S., Yoldi, M. E., Casasnovas, C., Willis, M. J. H., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci123959 · Cited by 99
“With progress in clinical genomics, new forms of ultra-rare leukodystrophies are being recognized (4-6), and advances in novel technologies in gene, cell and enzyme therapy hold promise for improving patient management (7, 8).”
BackgroundReady for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease
Ernst, M. P. T., Broeders, M., Herrero-Hernandez, P., Oussoren, E., van der Ploeg, A. T., & Pijnappel, W. W. M. P. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.06.022 · Cited by 103
Engineering an inhibitor-resistant human CSF1R variant for microglia replacement
Chadarevian, J. P., Lombroso, S. I., Peet, G. C., Hasselmann, J., Tu, C. H., Marzan, D. E., Capocchi, J. K., Purnell, F. S., Nemec, K. M., Lahian, A., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20220857 · Cited by 101
Gene therapy for CNS disorders: modalities, delivery and translational challenges
Gao, J., Gunasekar, S., Xia, Z. J., Shalin, K., Jiang, C., Chen, H., Lee, D., Lee, S., Pisal, N. D., Luo, J. N., et al. (2024) · Nature reviews. Neuroscience · doi:10.1038/s41583-024-00829-7 · Cited by 100
“For example, Skysona delivers a functional ABCD1 gene to individuals with cerebral adrenoleukodystro-phy 14 whereas other lentiviral vectors have been used to deliver a functional arylsulfatase A ( ARSA ) gene to individuals with metachromatic leukodystrophy 117 .”
Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy
Eichler, F., Duncan, C., Musolino, P. L., Lund, T. C., Gupta, A. O., Oliveira, S. N. D., Thrasher, A. J., Aubourg, P. R., Kühl, J., Loes, D. J., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2400442 · Cited by 103
Self-citationBergner, C. G., van der Meer, F., Winkler, A., Wrzos, C., Türkmen, M., Valizada, E., Fitzner, D., Hametner, S., Hartmann, C., Pfeifenbring, S., et al. (2019) · Glia · doi:10.1002/glia.23598 · Cited by 94
“However, the fact that these diseases partly respond to allogeneic or genetically modified autologous stem cell transplantation (Eichler et al., 2017; Kidd et al., 1998; Peters et al., 2004) underscores the fundamental importance of cells derived from—or replaceable by— descendants of the…”
BackgroundJensen, T. L., Gøtzsche, C. R., & Woldbye, D. P. D. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.695937 · Cited by 89
Lee, K., Abul‐Husn, N. S., Amendola, L. M., Brothers, K. B., Chung, W. K., Gollob, M. H., Gordon, A. S., Harrison, S. M., Hershberger, R. E., Li, M. M., et al. (2025) · Genetics in Medicine · doi:10.1016/j.gim.2025.101454 · Cited by 118
Update on Clinical Ex Vivo Hematopoietic Stem Cell Gene Therapy for Inherited Monogenic Diseases
Tucci, F., Scaramuzza, S., Aiuti, A., & Mortellaro, A. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.11.020 · Cited by 88
Ashrafi, M. R., Amanat, M., Garshasbi, M., Kameli, R., Nilipour, Y., Heidari, M., Rezaei, Z., & Tavasoli, A. R. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2020.1699060 · Cited by 83
Mallack, E. J., Turk, B. R., Yan, H., Price, C., Demetres, M., Moser, A. B., Becker, C., Hollandsworth, K., Adang, L., Vanderver, A., et al. (2021) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12356 · Cited by 79
“In addition, a recent clinical trial of autologous hematopoietic stem-cell gene therapy in boys with early-stage CCALD has produced encouraging results, and may soon become an additional treatment approach.(25,26) Given the limited window of time to intervene in CCALD, ALD newborn screening (NBS) was recently Synopsis”
BackgroundSelf-citationMusculoskeletal tissue engineering: Regional gene therapy for bone repair
Collon, K. W., Gallo, M. C., & Lieberman, J. R. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120901 · Cited by 80
Primary adrenal insufficiency in children: Diagnosis and management
Kırkgöz, T., & Güran, T. (2018) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2018.05.010 · Cited by 82
Autologous Stem-Cell-Based Gene Therapy for Inherited Disorders: State of the Art and Perspectives
Staal, F. J. T., Aiuti, A., & Cavazzana, M. (2019) · Frontiers in Pediatrics · doi:10.3389/fped.2019.00443 · Cited by 77
“X-Adrenoleukodystrophy (ALD) LV ABCD1 (35)”
BackgroundMuscle Atrophy: Present and Future
Cao, R. Y., Li, J., Dai, Q., Li, Q. X., & Yang, J. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1435-3_29 · Cited by 80
Brendel, C., Negre, O., Rothe, M., Guda, S., Parsons, G., Harris, C., McGuinness, M., Abriss, D., Tsytsykova, A., Klatt, D., et al. (2020) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2020.03.015 · Cited by 72
Self-citationChallenges in treating Pompe disease: an industry perspective
Hung, V., Khanna, R., & Gotschall, R. R. (2019) · Annals of Translational Medicine · doi:10.21037/atm.2019.04.15 · Cited by 74
“Proper ablation of bone marrow cells and engraftment of transduced HSCs are critical for maintaining a perpetual population of transduced progenitor stem cells for sustained production of therapeutic protein (96,97).”
BackgroundPeroxisomal ABC Transporters: An Update
Tawbeh, A., Gondcaille, C., Trompier, D., & Savary, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116093 · Cited by 68
“Lentiviral correction of bone marrow derived stem cells and autologous transplantation proved effective in 15 patients in 2017 [83].”
BackgroundDevelopment of Large-Scale Downstream Processing for Lentiviral Vectors
Valkama, A. J., Oruetxebarria, I., Lipponen, E. M., Leinonen, H. M., Käyhty, P., Hynynen, H., Turkki, V., Malinen, J., Miinalainen, T., Heikura, T., et al. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.03.025 · Cited by 71
The changing face of adrenoleukodystrophy
Zhu, J., Eichler, F., Biffi, A., Duncan, C. N., Williams, D. A., & Majzoub, J. A. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa013 · Cited by 78
Self-citationGenetic engineering meets hematopoietic stem cell biology for next-generation gene therapy
Ferrari, S., Valeri, E., Conti, A., Scala, S., Aprile, A., Micco, R. D., Kajaste‐Rudnitski, A., Montini, E., Ferrari, G., Aiuti, A., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.04.014 · Cited by 75
Wanders, R. J. A., Vaz, F. M., Waterham, H. R., & Ferdinandusse, S. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-60204-8_5 · Cited by 76
Weinhofer, I., Rommer, P. S., Zierfuss, B., Altmann, P., Foiani, M. S., Heslegrave, A., Zetterberg, H., Gleiß, A., Musolino, P. L., Gong, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22114-2 · Cited by 70
Self-citationTreatment of cerebral adrenoleukodystrophy: allogeneic transplantation and lentiviral gene therapy
Gupta, A. O., Raymond, G., Pierpont, E. I., Kemp, S., McIvor, R. S., Rayannavar, A., Miller, B., Lund, T. C., & Orchard, P. J. (2022) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2022.2124857 · Cited by 67
“However, it varied in design somewhat, including the removal of the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) [74,75].”
BackgroundMethodInfluentialSelf-citationPediatric Drug Development: Reviewing Challenges and Opportunities by Tracking Innovative Therapies
Domingues, C., Jarak, I., Veiga, F., Dourado, M., & Figueiras, A. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15102431 · Cited by 69
“Similar clinical benefits were observed in patients with Wiskott–Aldrich syndrome [230,231], X-linked adrenoleukodystrophy, metachromatic leukodystrophy [232,233], or transfusion dependent β -thalassemia [234–236] treated with lentiviral (LV) HSC therapy.”
ResultClonal selection of hematopoietic stem cells after gene therapy for sickle cell disease
Chapman, M. S., Cull, A. H., Ciuculescu, M. F., Esrick, E. B., Mitchell, E., Jung, H., O’Neill, L., Roberts, K., Fabre, M. A., Williams, N., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02636-6 · Cited by 66
Self-citationMishra, P., Silva, A., Sharma, J., Nguyen, J., Pizzo, D. P., Hinz, D., Sahoo, D., & Cherqui, S. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112956 · Cited by 64
“Finally, comprehensive understanding of the mechanism underlying the behavioral rescue in AD by WT HSPCs remains to be discovered.”
Gene therapy for primary immunodeficiency
Booth, C., Romano, R., Roncarolo, M. G., & Thrasher, A. J. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz170 · Cited by 63
Self-citationMallack, E. J., Gao, K., Engelen, M., & Kemp, S. (2022) · Cells · doi:10.3390/cells11020283 · Cited by 60
Functional correction of CFTR mutations in human airway epithelial cells using adenine base editors
Krishnamurthy, S., Traore, S., Cooney, A. L., Brommel, C. M., Kulhánková, K., Sinn, P. L., Newby, G. A., Liu, D. R., & McCray, P. B. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab788 · Cited by 63
“Recent successes in clinical trials for other genetic diseases (9–16) have renewed interest in gene therapy and gene editing approaches to treat or prevent CF lung disease (17–21), including gene addition approaches using viral and non-viral vectors for DNA and mRNA delivery (20– 25).”
Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease
Marquez Loza, L. I., Yuen, E. C., & McCray, P. B. (2019) · Genes · doi:10.3390/genes10030218 · Cited by 59
“In addition, in vivo somatic cell lentiviral gene therapy trials targeting the brain for MLD, X-ALD, and the retina for Stargardt’s macular degeneration and Usher syndrome type 1B are now underway.”
BackgroundInfluentialCurrent strategies for the treatment of inborn errors of metabolism
Gambello, M. J., & Li, H. (2018) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2018.02.001 · Cited by 59
Adrenoleukodystrophy: Guidance for adrenal surveillance in males identified by newborn screen
Regelmann, M. O., Kamboj, M. K., Miller, B. S., Nakamoto, J. M., Sarafoglou, K., Shah, S., Stanley, T. L., Marino, R., & Pediatric Endocrine Society Drug and Therapeutics/Rare Diseases Committee (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00920 · Cited by 61
Innate Immune Response to Viral Vectors in Gene Therapy
Wang, Y., & Shao, W. (2023) · Viruses · doi:10.3390/v15091801 · Cited by 65
Chandler, R. J., Venturoni, L. E., Liao, J., Hubbard, B. T., Schneller, J. L., Hoffmann, V. J., Gordo, S., Zang, S., Ko, C., Chau, N., et al. (2020) · Hepatology · doi:10.1002/hep.31570 · Cited by 57
Successful Preclinical Development of Gene Therapy for Recombinase-Activating Gene-1-Deficient SCID
García-Pérez, L., van Eggermond, M. C. J. A., van Roon, L., Vloemans, S. A., Cordes, M., Schambach, A., Rothe, M., Berghuis, D., Lagresle‐Peyrou, C., Cavazzana, M., et al. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.03.016 · Cited by 60
“The MND promoter has previously been used in gene therapy trials for ADA-SCID(50) and adrenoleukodystrophy (ALD), without any reports of insertional mutagenesis.(51,52) In the ALD trials there were some clones showing clonal dominance with over-representation of the insertion site near SMG6, CCND2, and HMGA2, but this…”
MethodSelf-citationLipids in the Physiopathology of Hereditary Spastic Paraplegias
Darios, F. D., Mochel, F., & Stévanin, G. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00074 · Cited by 55
Aberrant regulation of the GSK‐3β/NRF2 axis unveils a novel therapy for adrenoleukodystrophy
Ranea‐Robles, P., Launay, N., Ruíz, M., Calingasan, N. Y., Dumont, M., Naudí, A., Portero‐Otín, M., Pamplona, R., Ferrer, I., Beal, M. F., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708604 · Cited by 55
“…options are restricted to bone marrow transplantation (Miller et al, 2011) and hematopoietic stem cell gene therapy (Cartier et al, 2009; Eichler et al, 2017), and are limited by a very narrow therapeutic window, which reinforces the need to develop additional therapies for this…”
Gene Therapy for Spinal Muscular Atrophy: An Emerging Treatment Option for a Devastating Disease
Rao, V. K., Kapp, D., & Schroth, M. K. (2018) · Journal of Managed Care & Specialty Pharmacy · doi:10.18553/jmcp.2018.24.12-a.s3 · Cited by 62
Uchida, N., Stasula, U., Demirci, S., Germino-Watnick, P., Hinds, M., Le, A., Chu, R., Berg, A., Liu, X., Su, L., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41153-5 · Cited by 55
“Hematopoietic stem cell (HSC)-targeted gene therapy is potentially curative for multiple genetic diseases, including primary immunode-fi ciencies, hemoglobinopathies, and inherited metabolic disorders 1 – 4 .”
Lee, C. A. A., Seo, H. S., Armien, A. G., Bates, F. S., Tolar, J., & Azarin, S. M. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0094-5 · Cited by 52
Colella, P., Sayana, R., Suárez-Nieto, M. V., Sarno, J., Nyame, K., Xiong, J., Vera, L. N. P., Basurto, J. A., Corbo, M., Limaye, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49908-4 · Cited by 56
Long-term lineage commitment in haematopoietic stem cell gene therapy
Calabria, A., Spinozzi, G., Cesana, D., Buscaroli, E., Benedicenti, F., Pais, G., Gazzo, F., Scala, S., Lidonnici, M. R., Scaramuzza, S., et al. (2024) · Nature · doi:10.1038/s41586-024-08250-x · Cited by 55
Lipid nanoparticle-mediated mRNA delivery to CD34+ cells in rhesus monkeys
Kim, H., Zenhausern, R., Gentry, K., Lian, L., Huayamares, S. G., Radmand, A., Loughrey, D., Podilapu, A. R., Hatit, M. Z. C., Ni, H., et al. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02470-2 · Cited by 59
Poletti, V., Charrier, S., Corre, G., Gjata, B., Vignaud, A., Zhang, F., Rothe, M., Schambach, A., Gaspar, H. B., Thrasher, A. J., et al. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.03.002 · Cited by 51
Self-citationSchott, J. W., León‐Rico, D., Ferreira, C. B., Buckland, K. F., Santilli, G., Armant, M. A., Schambach, A., Cavazza, A., & Thrasher, A. J. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.05.015 · Cited by 54
“13 Disorders of the hematopoietic system are especially suitable for gene therapy due to the unique hierarchy of the blood system, with the hematopoietic stem cell (HSC) being able to reconstitute all blood lineages and self-renew, providing potential for a lifelong cure.”
Self-citationAdhikari, A., Copping, N. A., Beegle, J. R., Cameron, D. L., Deng, P., O’Geen, H., Segal, D. J., Fink, K. D., Silverman, J. L., & Anderson, J. S. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab104 · Cited by 52
“Four treatment groups were analyzed for prevention or functional rescue in behavioral assays relevant to AS and reproduced rigorously in our laboratory and others (31,36,37).”
BackgroundMethodGene Therapy Developments for Pompe Disease
Unnisa, Z., Yoon, J. K., Schindler, J. W., Mason, C., & van Til, N. P. (2022) · Biomedicines · doi:10.3390/biomedicines10020302 · Cited by 53
An update on gene therapy for lysosomal storage disorders
Nagree, M. S., Scalia, S., McKillop, W. M., & Medin, J. A. (2019) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2019.1607837 · Cited by 50
“In that trial, hematopoietic-derived cells migrated into the CNS, persisted, and provided ‘factories’ of functional ABCD1, providing clinical benefit years following transplant [41].”
BackgroundInfluentialClinical translation of gene medicine
Wang, F., Qin, Z., Lu, H., He, S., Luo, J. C., Jin, C., & Song, X. (2019) · The Journal of Gene Medicine · doi:10.1002/jgm.3108 · Cited by 48
Modeling CSF‐1 receptor deficiency diseases – how close are we?
Chiţu, V., Gökhan, Ş., & Stanley, E. R. (2021) · FEBS Journal · doi:10.1111/febs.16085 · Cited by 48
Gene Editing of Hematopoietic Stem Cells: Hopes and Hurdles Toward Clinical Translation
Ferrari, S., Vavassori, V., Canarutto, D., Jacob, A., Castiello, M. C., Omer, A., & Genovese, P. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.618378 · Cited by 52
“For instance, up to 105 cells in the drug product might have unmeasurable nuclease activity at an off-target site considering the dose of edited HSPCs commonly administered in gene therapy settings (from 107 to 109) (Gaspar et al., 2011; Sessa et al., 2016; Eichler et al., 2017; Thompson et al., 2018; Ferrua et al., 2…”
BackgroundIn vivo dynamics of human hematopoietic stem cells: novel concepts and future directions
Scala, S., & Aiuti, A. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019000039 · Cited by 57
Page, K. M., Stenger, E. O., Connelly, J. A., Shyr, D. C., West, T., Wood, S. J., Case, L. E., Kester, M., Shim, S., Hammond, L., et al. (2019) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2019.09.003 · Cited by 49
Recent trends in mucopolysaccharidosis research
Kobayashi, H. (2018) · Journal of Human Genetics · doi:10.1038/s10038-018-0534-8 · Cited by 51
Current Insights Into Adrenal Insufficiency in the Newborn and Young Infant
Buonocore, F., McGlacken-Byrne, S. M., del Valle, I., & Achermann, J. C. (2020) · Frontiers in Pediatrics · doi:10.3389/fped.2020.619041 · Cited by 53
Evolution of Gene Therapy, Historical Perspective
Malech, H. L., Garabedian, E., & Hsieh, M. M. (2022) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2022.05.001 · Cited by 51
Kühl, J., Kupper, J., Baqué, H., Ebell, W., Gärtner, J., Korenke, G. C., Spors, B., Steffen, I. G., Strauß, G., Voigt, S., et al. (2018) · JAMA Network Open · doi:10.1001/jamanetworkopen.2018.0769 · Cited by 44
“Among the symptomatic patients, 11 of 18 (61%) survived, but only 1 was EFS (6%) (median [IQR] EFS time, 9 [3-22] months).”
Piguet, F., Saint-Denis, T. D., Audouard, E., Beccaria, K., André, A., Wurtz, G., Schatz, R., Alves, S., Sevin, C., Zérah, M., et al. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.105 · Cited by 47
“21,22 In LSDs, donor-derived microglia cells of myeloid origin are thought to be the source of enzyme after HSCT, cross-correcting the metabolic defect in affected host cells.”
Self-citationTherapy Development by Genome Editing of Hematopoietic Stem Cells
Koniali, L., Lederer, C. W., & Kleanthous, M. (2021) · Cells · doi:10.3390/cells10061492 · Cited by 50
“Early clinical trials demonstrated safety and efficacy of viral-mediated permanent gene transfer for multiple life-threatening or orphan blood disorders, including congenital hematopoietic disorders: sickle cell disease (SCD) and β-thalassemia [10–13]; Fanconi anemia (FA) [14]; immunodeficiencies, Wiskott–Aldrich synd…”
BackgroundIntrathecal Adeno-Associated Viral Vector-Mediated Gene Delivery for Adrenomyeloneuropathy
Gong, Y., Berenson, A., Laheji, F., Gao, G., Wang, D., Ng, C., Volak, A., Kok, R., Kreouzis, V., Dijkstra, I. M., et al. (2019) · Human Gene Therapy · doi:10.1089/hum.2018.079 · Cited by 45
“Further testing in nonhuman primates may enable the development of intrathecal AAV9-ABCD1 as a gene therapy for AMN.”
BackgroundMethodInfluentialSelf-citationElivaldogene Autotemcel: First Approval
Keam, S. J. (2021) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-021-00555-1 · Cited by 44
“Elivaldogene autotemcel is a genetically modified autologous CD34+ cell-enriched population that contains HSCs transduced ex vivo with the LVV encoding the human ABCD1 complementary deoxyribonucleic acid (cDNA) for ALDP [2, 9].”
BackgroundResultInfluentialLong-Term Follow-Up of Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy
Bougnères, P., Hacein-Bey-Abina, S., Labik, I., Adamsbaum, C., Castaignède, C., Bellesme, C., & Schmidt, M. (2021) · Human Gene Therapy · doi:10.1089/hum.2021.053 · Cited by 45
Metadata
- Authors
- Eichler, F., Duncan, C., Musolino, P. L., Orchard, P. J., De Oliveira, S., Thrasher, A. J., Armant, M., Dansereau, C., Lund, T. C., Miller, W. P., Raymond, G. V., Sankar, R., Shah, A. J., Sevin, C., Gaspar, H. B., Gissen, P., Amartino, H., Bratkovic, D., Smith, N. J. C., Paker, A. M., Shamir, E., O’Meara, T., Davidson, D., Aubourg, P., & Williams, D. A.
- Affiliations
- Boston Children's Hospital (US)
- Bluebird Bio (United States) (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-10-26
- Volume
- 377
- Issue
- 17
- Pages
- 1630-1638
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC5708849
- OpenAlex
- W2764213443
- Cited by
- 604
- References
- 31
- Citations by year
- 2026: 47 · 2025: 43 · 2024: 96 · 2023: 60 · 2022: 67 · 2021: 79 · 2020: 60 · 2019: 75 · 2018: 63 · 2017: 11
- FWCI
- 37.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Wellcome Trust (104807/Z/14/Z)
- National Institutes of Health (UL1TR001102)
- National Institute of Neurological Disorders and Stroke (K08NS094683)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- cerebral adrenoleukodystrophy, X-linked adrenoleukodystrophy, ABCD1, hematopoietic stem cell gene therapy, lentiviral vectors, demyelination, neurodegeneration, graft-versus-host disease, functional disability, early-stage disease
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily D, Member 1, Adolescent, Adrenoleukodystrophy, Child, Combined Modality Therapy, Genetic Vectors, Hematopoietic Stem Cells, Humans, Male, Transplantation, Autologous, Genetic Therapy, Biomarkers, Lentivirus, Polymerase Chain Reaction, Granulocyte Colony-Stimulating Factor, Hematopoietic Stem Cell Transplantation, ATP-Binding Cassette Transporters, Antigens, CD34
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
