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 Another patient, who had had evidence of disease progression on MRI, had withdrawn from the study to undergo allogeneic stem-cell transplantation and later died from transplantation-related complications.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 .).
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Both hematopoietic stem cell transplantation and gene therapy require the patient to undergo chemotherapy.
“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]
The Methods (Study Design and Investigational Therapy; page unavailable) state that patients receiving Lenti-D gene therapy were conditioned with busulfan and cyclophosphamide before infusion. The Discussion says allogeneic transplantation requires immunosuppression, but the passages found do not state that transplantation requires chemotherapy. The paper therefore supports the gene-therapy part of the claim, not the assertion that both require chemotherapy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredEarly-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.
“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]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe well-established treatments for CALD are useful only as the first signs of abnormalities are noted on MRI, before the onset of any neurological symptoms.
“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]
The introductory passage following the Abstract > Conclusions says transplantation is more likely to be effective early and reports good outcomes when disease is detected by imaging before symptoms. It does not say treatment is useful only at that point: it describes outcomes in symptomatic boys with a high burden of disease as often unfavorable, not invariably so. (LLM, conf=0.87)
Experimental — accuracy not yet measuredPrompt diagnosis can improve the prognosis of CALD in boys.
“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]
Autologous hematopoietic stem cell transplantation after ex vivo lentiviral gene therapy has been developed.
“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 c.901-25_901-9 del variant was classified as a VUS according to the ACMG PM2, PP3, and PP4 criteria.
“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]
The Methods section on clinical, imaging, and laboratory assessments describes PCR analysis of vector integration sites, not classification of the c.901-25_901-9 del variant. Searches for the variant and for ACMG, VUS, and Sanger sequencing found no passage addressing the claimed classification. (LLM, conf=0.74)
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Designing Lentiviral Vectors for Gene Therapy of Genetic Diseases
Poletti, V., & Mavilio, F. (2021) · Viruses · doi:10.3390/v13081526 · Cited by 105 · see citing works
“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 · see citing works
“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
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Engineering an inhibitor-resistant human CSF1R variant for microglia replacement
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Gene therapy for CNS disorders: modalities, delivery and translational challenges
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“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 94 · see citing works
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“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 85 · see citing works
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Update on Clinical Ex Vivo Hematopoietic Stem Cell Gene Therapy for Inherited Monogenic Diseases
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“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 78 · see citing works
Primary adrenal insufficiency in children: Diagnosis and management
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Autologous Stem-Cell-Based Gene Therapy for Inherited Disorders: State of the Art and Perspectives
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“X-Adrenoleukodystrophy (ALD) LV ABCD1 (35)”
BackgroundMuscle Atrophy: Present and Future
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Self-citationChallenges in treating Pompe disease: an industry perspective
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“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
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“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 · see citing works
The changing face of adrenoleukodystrophy
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Self-citationGenetic engineering meets hematopoietic stem cell biology for next-generation gene therapy
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Self-citationTreatment of cerebral adrenoleukodystrophy: allogeneic transplantation and lentiviral gene therapy
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“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 64 · see citing works
“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 65 · see citing works
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“Finally, comprehensive understanding of the mechanism underlying the behavioral rescue in AD by WT HSPCs remains to be discovered.”
Gene therapy for primary immunodeficiency
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Self-citationMallack, E. J., Gao, K., Engelen, M., & Kemp, S. (2022) · Cells · doi:10.3390/cells11020283 · Cited by 60 · see citing works
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 61 · see citing works
“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).”
Current strategies for the treatment of inborn errors of metabolism
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Adrenoleukodystrophy: Guidance for adrenal surveillance in males identified by newborn screen
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Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease
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“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.”
BackgroundInfluentialInnate Immune Response to Viral Vectors in Gene Therapy
Wang, Y., & Shao, W. (2023) · Viruses · doi:10.3390/v15091801 · Cited by 60 · see citing works
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 · see citing works
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 56 · see citing works
“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 56 · see citing works
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 · see citing works
“…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 55 · see citing works
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“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 · see citing works
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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 53 · see citing works
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 56 · see citing works
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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 49 · see citing works
“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 49 · see citing works
“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 52 · see citing works
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 · see citing works
“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 49 · see citing works
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 50 · see citing works
Gene Editing of Hematopoietic Stem Cells: Hopes and Hurdles Toward Clinical Translation
Ferrari, S., Vavassori, V., Canarutto, D., Jacob, A., Castiello, M. C., Javed, A. O., & Genovese, P. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.618378 · Cited by 38 · see citing works
“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 47 · see citing works
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 · see citing works
Recent trends in mucopolysaccharidosis research
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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 51 · see citing works
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 47 · see citing works
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 45 · see citing works
“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 44 · see citing works
“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 46 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
- 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 · 2015: 1 · 2013: 1
- 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 › Physiology › 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 ›
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