Treatment of cerebral adrenoleukodystrophy: allogeneic transplantation and lentiviral gene therapy
Open accessAbstract
INTRODUCTION: gene. By adulthood, approximately 40% of the patients develop cerebral ALD, a severe, neuroinflammatory condition that is generally progressive and fatal without intervention. AREAS COVERED: Historically, only allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to halt progression of cerebral ALD, with superior outcomes obtained when HSCT is performed early in the disease process. More recently, a lentiviral-based gene therapy approach has been investigated as therapy for cerebral ALD as an alternative to allogeneic transplantation. A focused literature review was performed using the terms 'hematopoietic stem cell transplantation,' 'gene therapy' and 'adrenoleukodystrophy' to include relevant literature, especially comparing the experience with gene therapy and HSCT outcomes. We review the history and experience with HSCT in cerebral ALD and its limitations, as well as the information currently available in association with the gene therapy trials for cerebral ALD. EXPERT OPINION: The data regarding this lentiviral-based gene therapy approach and its relative risks and benefits is still being evaluated. This information is explored in the context of the experience with allogeneic HSCT for cerebral ALD.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
After HCT or gene therapy, improvement in disease burden is usually not observed, and stop or minimization of progression represent the primary therapeutic goals.
“Improvement in disease burden is usually not observed, and stop or minimization of progression represent the primary therapeutic goals (49).”
From X-linked adrenoleukodystrophy and primary adrenal insufficiency (2023) · cites this paper as [49]
Cites
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 · cited 1× · see citing works
“by administration of granulocyte-colony stimulating factor (G-CSF) in 2 boys with cerebral ALD [69].”
BackgroundEpidemiology of childhood cancer
Kaatsch, P. (2010) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2010.02.003 · Cited by 981 · see citing works
Clinical use of lentiviral vectors
Milone, M. C., & O’Doherty, U. (2018) · Leukemia · doi:10.1038/s41375-018-0106-0 · Cited by 930 · see citing works
Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy
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., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1700554 · Cited by 604 · cited 6× · see citing works
“However, it varied in design somewhat, including the removal of the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) [74,75].”
BackgroundMethodInfluentialSelf-citationSessa, M., Lorioli, L., Fumagalli, F., Acquati, S., Redaelli, D., Baldoli, C., Canale, S., Lopez, I. D., Morena, F., Calabria, A., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30374-9 · Cited by 502 · see citing works
HOBBS, J. (1981) · The Lancet · doi:10.1016/s0140-6736(81)91046-1 · Cited by 495 · see citing works
Adrenoleukodystrophy: A Clinical and Pathological Study of 17 Cases
Schaumburg, H. H. (1975) · Archives of Neurology · doi:10.1001/archneur.1975.00490510033001 · Cited by 475 · see citing works
Successful Bone-Marrow Transplantation for Infantile Malignant Osteopetrosis
Coccia, P. F., Krivit, W. A., Červenka, J., Clawson, C., Kersey, J. H., Kim, T. H., Nesbit, M. E., Ramsay, N. K. C., Warkentin, P. I., Teitelbaum, S. L., et al. (1980) · New England Journal of Medicine · doi:10.1056/nejm198003273021301 · Cited by 450 · see citing works
Hurler and Hunter Syndromes: Mutual Correction of the Defect in Cultured Fibroblasts
Fratantoni, J. C., Hall, C. W., & Neufeld, E. F. (1968) · Science · doi:10.1126/science.162.3853.570 · Cited by 446 · cited 1× · see citing works
“provide ‘cross correction’ of adjacent cells as was initially demonstrated by Neufeld’s group in lysosomal disease [62].”
BackgroundPeters, C., Charnas, L. R., Tan, Y., Ziegler, R. S., Shapiro, E. G., DeFor, T., Grewal, S. S., Orchard, P. J., Abel, S. L., Goldman, A. I., et al. (2004) · Blood · doi:10.1182/blood-2003-10-3402 · Cited by 374 · see citing works
Self-citationAubourg, P., Blanche, S., Jambaqué, I., Rocchiccioli, F., Kalifa, G., Naud-Saudreau, C., Rolland, M.-O., Debré, M., Chaussain, J.-L., Griscelli, C., et al. (1990) · New England Journal of Medicine · doi:10.1056/nejm199006283222607 · Cited by 366 · cited 1× · see citing works
“the experience in transplantation of an 8-year-old boy diagnosed with ALD following adrenal crisis, who later developed white matter changes in the internal capsule [49].”
BackgroundKemp, S., Pujol, A., Waterham, H. R., van Geel, B. M., Boehm, C. D., Raymond, G. V., Cutting, G. R., Wanders, R. J. A., & Moser, H. W. (2001) · Human Mutation · doi:10.1002/humu.1227 · Cited by 332 · see citing works
Self-citationAdrenoleukodystrophy: Incidence, new mutation rate, and results of extended family screening
Bezman, L., Moser, A. B., Raymond, G. V., Rinaldo, P., Watkins, P. A., Smith, K. D., Kass, N. E., & Moser, H. W. (2001) · Annals of Neurology · doi:10.1002/ana.101 · Cited by 324 · see citing works
Self-citationFumagalli, F., Calbi, V., Sora, M. G. N., Sessa, M., Baldoli, C., Rancoita, P. M. V., Ciotti, F., Sarzana, M., Fraschini, M., Zambon, A. A., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(21)02017-1 · Cited by 299 · see citing works
A mouse model for X-linked adrenoleukodystrophy
Lu, J.-F., Lawler, A. M., Watkins, P. A., Powers, J. M., Moser, A. B., Moser, H. W., & Smith, K. D. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.17.9366 · Cited by 293 · see citing works
Miller, W. P., Rothman, S. M., Nascene, D., Kivisto, T., DeFor, T. E., Ziegler, R. S., Eisengart, J., Leiser, K., Raymond, G., Lund, T. C., et al. (2011) · Blood · doi:10.1182/blood-2011-01-329235 · Cited by 290 · cited 1× · see citing works
“transplant regiments, may be helpful as a means of increasing survival, particularly in patients with more advanced disease [54,55].”
BackgroundSelf-citationX-linked adrenoleukodystrophy: Clinical, metabolic, genetic and pathophysiological aspects
Kemp, S., Berger, J., & Aubourg, P. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.03.012 · Cited by 283 · see citing works
Self-citationAdrenoleukodystrophy—Neuroendocrine pathogenesis and redefinition of natural history
Kemp, S., Huffnagel, I. C., Linthorst, G. E., Wanders, R. J., & Engelen, M. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.90 · Cited by 275 · see citing works
Self-citationAnalysis of MRI patterns aids prediction of progression in X-linked adrenoleukodystrophy
Loes, D. J., Fatemi, A., Melhem, E. R., Gupte, N., Bezman, L., Moser, H. W., & Raymond, G. V. (2003) · Neurology · doi:10.1212/01.wnl.0000079050.91337.83 · Cited by 268 · see citing works
Self-citationAdrenoleukodystrophy: Survey of 303 cases: Biochemistry, diagnosis, and therapy
Moser, H. W., Moser, A. E., Singh, I., & OʼNeill, P. (1984) · Annals of Neurology · doi:10.1002/ana.410160603 · Cited by 259 · cited 1× · see citing works
“VLCFA; however, the gene product had not yet been identified, and was thought to be an enzyme defect in the early steps of peroxisomal beta oxidation [42].”
BackgroundPedersen-Bjergaard, J., Andersen, M. K., & Christiansen, D. H. (2000) · Blood · doi:10.1182/blood.v95.11.3273 · Cited by 244 · cited 1× · see citing works
“5 years) after autologous HSCT in patients who had received prior chemotherapy with alkylating agents and radiation [81,82].”
BackgroundFollow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo's oil
Moser, H. W., Raymond, G. V., Lu, S.-E., Muenz, L. R., Moser, A. B., Xu, J., Jones, R. O., Loes, D. J., Melhem, E. R., Dubey, P., et al. (2005) · Archives of Neurology · doi:10.1001/archneur.62.7.1073 · Cited by 239 · cited 2× · see citing works
“Reproduced with permission from [41], © 2005 American Medical Association.”
BackgroundMethodSelf-citationAdrenoleukodystrophy: Phenotypic variability and implications for therapy
Moser, H. W., Moser, A. B., Smith, K. D., Bergin, A., Borel, J., Shankroff, J., Stine, O. C., Merette, C., Ott, J., Krivit, W., et al. (1992) · Journal of Inherited Metabolic Disease · doi:10.1007/bf01799621 · Cited by 239 · see citing works
X-linked adrenoleukodystrophy in women: A cross-sectional cohort study
Engelen, M., Barbier, M., Dijkstra, I. M. E., Schür, R., de Bie, R. M. A., Verhamme, C., Dijkgraaf, M. G. W., Aubourg, P. A., Wanders, R. J. A., van Geel, B. M., et al. (2014) · Brain · doi:10.1093/brain/awt361 · Cited by 234 · see citing works
Self-citationPujol, A. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.5.499 · Cited by 214 · see citing works
Early oxidative damage underlying neurodegeneration in X-adrenoleukodystrophy
Fourcade, S., Lopez-Erauskin, J., Galino, J., Duval, C., Naudi, A., Jove, M., Kemp, S., Villarroya, F., Ferrer, I., Pamplona, R., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn085 · Cited by 214 · cited 1× · see citing works
“a role in the pathophysiology of progression in cerebral disease [52,53], interventions such as N-acetylcysteine were explored.”
BackgroundSelf-citationAcute Myeloid Leukemia Case after Gene Therapy for Sickle Cell Disease
Goyal, S., Tisdale, J., Schmidt, M., Kanter, J., Jaroscak, J., Whitney, D., Bitter, H., Gregory, P. D., Parsons, G., Foos, M., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2109167 · Cited by 212 · cited 3× · see citing works
“after treatment on a trial utilizing the BB305 lentiviral vector encoding the -globin gene (HGB-206 Study) [85,86].”
BackgroundMethodChallita, P. M., Skelton, D. C., El-Khoueiry, A. B., Yu, X., Weinberg, K. I., & Kohn, D. B. (1995) · Journal of Virology · doi:10.1128/jvi.69.2.748-755.1995 · Cited by 209 · see citing works
Turk, B. R., Theda, C., Fatemi, A. S., & Moser, A. B. (2020) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.10003 · Cited by 206 · see citing works
Long-term complications after hematopoietic cell transplantation
Majhail, N. S. (2017) · Hematology/Oncology and Stem Cell Therapy · doi:10.1016/j.hemonc.2017.05.009 · Cited by 202 · see citing works
Bone-Marrow Transplantation in the Maroteaux–Lamy Syndrome (Mucopolysaccharidosis Type VI)
Krivit, W. A., Pierpont, M. E., Ayaz, K. L., Tsai, M. Y., Ramsay, N. K. C., Kersey, J. H., Weisdorf, S., Sibley, R. K., Snover, D. C., McGovern, M. M., et al. (1984) · New England Journal of Medicine · doi:10.1056/nejm198412203112504 · Cited by 199 · see citing works
Hubbard, W. C., Moser, A. B., Liu, A. C., Jones, R. O., Steinberg, S. J., Lorey, F., Panny, S. R., Vogt Jr., R. F., Macaya, D., & Turgeon, C. T. (2009) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2009.03.010 · Cited by 177 · cited 1× · see citing works
“spots [12], and subsequently high-throughput measures were published [13,14].”
BackgroundThe role of ELOVL1 in very long-chain fatty acid homeostasis and X-linked adrenoleukodystrophy
Ofman, R., Dijkstra, I. M. E., van Roermund, C. W. T., Burger, N., Turkenburg, M., van Cruchten, A., van Engen, C. E., Wanders, R. J. A., & Kemp, S. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000061 · Cited by 170 · cited 1× · see citing works
“concentrations of saturated VLCFA >C22:0 are observed [5,6].”
BackgroundSelf-citationHsieh, M. M., Bonner, M., Pierciey, F. J., Uchida, N., Rottman, J., Demopoulos, L., Schmidt, M., Kanter, J., Walters, M. C., Thompson, A. A., et al. (2020) · Blood Advances · doi:10.1182/bloodadvances.2019001330 · Cited by 152 · cited 2× · see citing works
“after treatment on a trial utilizing the BB305 lentiviral vector encoding the -globin gene (HGB-206 Study) [85,86].”
MethodHuffnagel, I. C., Laheji, F. K., Aziz-Bose, R., Tritos, N. A., Marino, R., Linthorst, G. E., Kemp, S., Engelen, M., & Eichler, F. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01307 · Cited by 147 · cited 1× · see citing works
“Adrenal insufficiency develops in approximately 80% of patients with ALD [19], but often this is an isolated glucocorticoid deficiency due to preferential accumulation of VLCFA in the adrenal zona fasciculata where”
BackgroundSelf-citationIncreased risk of leukemia among sickle cell disease patients in California
Brunson, A. M., Keegan, T. H. M., Bang, H., Mahajan, A., Paulukonis, S. T., & Wun, T. (2017) · Blood · doi:10.1182/blood-2017-05-783233 · Cited by 146 · cited 1× · see citing works
“disease might be at a higher risk of developing leukemia than the general population at baseline [87].”
BackgroundHalene, S., Wang, L., Cooper, R. M., Bockstoce, D. C., Robbins, P. B., & Kohn, D. B. (1999) · Blood · doi:10.1182/blood.v94.10.3349.422k05_3349_3357 · Cited by 145 · see citing works
Tucci, F., Galimberti, S., Naldini, L., Valsecchi, M. G., & Aiuti, A. (2022) · Nature Communications · doi:10.1038/s41467-022-28762-2 · Cited by 144 · cited 1× · see citing works
“tional mutagenesis across 55 studies including a total of 406 participants using lentiviral and gammaretroviral vectors [89].”
BackgroundRaymond, 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 · cited 2× · see citing works
“incontinence, or lack of voluntary movement [56].”
BackgroundSelf-citationRome, L. H., Weissmann, B., & Neufeld, E. F. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.5.2331 · Cited by 139 · cited 1× · see citing works
“internalized by deficient cells through association with mannose-6-phosphate receptors [60,61].”
BackgroundAdreno-leukodystrophy: Oxidative Stress of Mice and Men
Powers, J. M., Pei, Z., Heinzer, A. K., Brose, R. D., Moser, A. B., Moser, H. W., Watkins, P. A., & Smith, K. D. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000190064.28559.a4 · Cited by 131 · cited 1× · see citing works
“a role in the pathophysiology of progression in cerebral disease [52,53], interventions such as N-acetylcysteine were explored.”
BackgroundLentiviral Hematopoietic Cell Gene Therapy for X-Linked Adrenoleukodystrophy
Cartier, N., Hacein-Bey-Abina, S., Bartholomae, C. C., Bougnères, P., Schmidt, M., Von Kalle, C., Fischer, A., Cavazzana-Calvo, M., & Aubourg, P. (2012) · Methods in Enzymology · doi:10.1016/b978-0-12-386509-0.00010-7 · Cited by 123 · cited 1× · see citing works
“There have been two subsequent reports regarding this study, which encompassed a total of 4 patients [72,73].”
ResultKemp, S., Theodoulou, F. L., & Wanders, R. J. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01435.x · Cited by 115 · cited 1× · see citing works
“However, several missense variants have been reported that do not affect protein stability, but disrupt the protein’s function by decreasing ATPbinding capacity or ATPase activity [110].”
BackgroundSelf-citationBone marrow transplant in adrenoleukodystrophy
Moser, H. W., Tutschka, P. J., Brown, F. R., Moser, A. E., Yeager, A. M., Singh, I., Mark, S. A., Kumar, A., McDonnell, J. M., White, C. L., et al. (1984) · Neurology · doi:10.1212/wnl.34.11.1410 · Cited by 107 · see citing works
BONE MARROW TRANSPLANTATION FOR INBORN ERRORS
HOBBS, J. (1981) · The Lancet · doi:10.1016/s0140-6736(81)91059-x · Cited by 107 · see citing works
Treating Immunodeficiency through HSC Gene Therapy
Booth, C., Gaspar, H. B., & Thrasher, A. J. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.02.002 · Cited by 106 · cited 1× · see citing works
“vectors were subsequently determined to have a predilection to insert near transcriptional regulatory regions, potentially resulting in ‘insertional oncogenesis’ [83].”
BackgroundNewborn Screening for X-Linked Adrenoleukodystrophy
Moser, A., Jones, R., Hubbard, W., Tortorelli, S., Orsini, J., Caggana, M., Vogel, B., & Raymond, G. (2016) · International Journal of Neonatal Screening · doi:10.3390/ijns2040015 · Cited by 106 · cited 2× · see citing works
“In February of 2016 Secretary Burwell signed the letter of approval to add ALD to the Recommended Uniform Screening Panel [11].”
BackgroundSelf-citationChow, E. J., Simmons, J. H., Roth, C. L., Baker, K. S., Hoffmeister, P. A., Sanders, J. E., & Friedman, D. L. (2010) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2010.05.016 · Cited by 104 · cited 1× · see citing works
“These regimens have known long-term toxicities such as hormonal dysfunction, pulmonary insufficiency, sterility, and metabolic syndrome [79,80].”
BackgroundDisease progression in women with X-linked adrenoleukodystrophy is slow
Huffnagel, I. C., Dijkgraaf, M. G. W., Janssens, G. E., van Weeghel, M., van Geel, B. M., Poll-The, B. T., Kemp, S., & Engelen, M. (2019) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-019-1008-6 · Cited by 100 · cited 1× · see citing works
“affected women show symptoms in adulthood related to spinal cord involvement [15,16].”
BackgroundSelf-citationFrequent occurrence of cerebral demyelination in adrenomyeloneuropathy
de Beer, M., Engelen, M., & van Geel, B. M. (2014) · Neurology · doi:10.1212/wnl.0000000000001074 · Cited by 97 · see citing works
Elongation of very long-chain fatty acids is enhanced in X-linked adrenoleukodystrophy
Kemp, S., Valianpour, F., Denis, S., Ofman, R., Sanders, R.-J., Mooyer, P., Barth, P. G., & Wanders, R. J. A. (2005) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2004.09.015 · Cited by 97 · cited 1× · see citing works
“concentrations of saturated VLCFA >C22:0 are observed [5,6].”
BackgroundSelf-citationPerkins, J. L., Kunin‐Batson, A., Youngren, N. M., Ness, K. K., Ulrich, K. J., Hansen, M. J., Petryk, A., Steinberger, J., Anderson, F. S., & Baker, K. S. (2007) · Pediatric Blood & Cancer · doi:10.1002/pbc.21207 · Cited by 96 · cited 1× · see citing works
“These regimens have known long-term toxicities such as hormonal dysfunction, pulmonary insufficiency, sterility, and metabolic syndrome [79,80].”
BackgroundPowers, J. M. (1974) · Archives of Neurology · doi:10.1001/archneur.1974.00490350064011 · Cited by 94 · see citing works
Gene therapy for leukodystrophies
Biffi, A., Aubourg, P. R., & Cartier, N. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr142 · Cited by 94 · see citing works
van Geel, B. M., Poll‐The, B. T., Verrips, A., Boelens, J., Kemp, S., & Engelen, M. (2015) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-014-9797-1 · Cited by 78 · cited 4× · see citing works
“Additionally, in cases where an individual underwent HSCT for advanced cerebral ALD, the clinical findings associated with AMN might prove difficult to distinguish from the neurologic manifestations with advanced cerebral disease.”
InfluentialSelf-citationThe 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 · cited 2× · see citing works
“what, including the removal of the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) [74,75].”
BackgroundMetachromatic leukodystrophy: A single‐center longitudinal study of 45 patients
Fumagalli, F., Zambon, A. A., Rancoita, P. M. V., Baldoli, C., Canale, S., Spiga, I., Medaglini, S., Penati, R., Facchini, M., Ciotti, F., et al. (2021) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12388 · Cited by 75 · see citing works
Treatment of brain disease in the mucopolysaccharidoses
Scarpa, M., Orchard, P. J., Schulz, A., Dickson, P., Haskins, M. E., Escolar, M. L., & Giugliani, R. (2017) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2017.10.007 · Cited by 72 · see citing works
Self-citationJaspers, Y. R. J., Ferdinandusse, S., Dijkstra, I. M. E., Barendsen, R. W., van Lenthe, H., Kulik, W., Engelen, M., Goorden, S. M. I., Vaz, F. M., & Kemp, S. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00690 · Cited by 69 · cited 1× · see citing works
“a sensitivity of >99% in diagnosing women with ALD, including those with normal plasma VLCFA levels [9].”
BackgroundSelf-citationMoser, H. W., Raymond, G. V., Köehler, W., Sokolowski, P., Hanefeld, F. A., Korenke, G. C., Green, A., Loes, D. J., HUNNEMAN, D. H., Jones, R. O., et al. (2003) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-9072-3_47 · Cited by 63 · see citing works
Self-citationX‐linked adrenoleukodystrophy: Therapeutic approaches to distinct phenotypes
Mahmood, A., Dubey, P., Moser, H. W., & Moser, A. B. (2005) · Pediatric Transplantation · doi:10.1111/j.1399-3046.2005.00447.x · Cited by 63 · see citing works
Pierpont, E. I., Eisengart, J. B., Shanley, R., Nascene, D., Raymond, G. V., Shapiro, E. G., Ziegler, R. S., Orchard, P. J., & Miller, W. P. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.0013 · Cited by 62 · cited 1× · see citing works
“cognitive outcomes and less independent function after HSCT [39,58].”
BackgroundSelf-citationBenhamida, S., Pflumio, F., Dubart-Kupperschmitt, A., Zhao-Emonet, J.-C., Cavazzana-Calvo, M., Rocchiccioli, F., Fichelson, S., Aubourg, P., Charneau, P., & Cartier, N. (2003) · Molecular Therapy · doi:10.1016/s1525-0016(03)00002-9 · Cited by 61 · cited 1× · see citing works
“an internal elongation factor 1 promoter [68].”
Mallack, E. J., Gao, K., Engelen, M., & Kemp, S. (2022) · Cells · doi:10.3390/cells11020283 · Cited by 60 · see citing works
Self-citationTurgeon, C. T., Moser, A. B., Mørkrid, L., Magera, M. J., Gavrilov, D. K., Oglesbee, D., Raymond, K., Rinaldo, P., Matern, D., & Tortorelli, S. (2015) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2014.11.013 · Cited by 60 · cited 1× · see citing works
“spots [12], and subsequently high-throughput measures were published [13,14].”
BackgroundTheda, C., Gibbons, K., DeFor, T. E., Donohue, P. K., Golden, W. C., Kline, A. D., Gulamali-Majid, F., Panny, S. R., Hubbard, W. C., Jones, R. O., et al. (2014) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2013.10.019 · Cited by 56 · cited 1× · see citing works
“spots [12], and subsequently high-throughput measures were published [13,14].”
BackgroundSelf-citationN-acetyl-L-cysteine improves outcome of advanced cerebral adrenoleukodystrophy
Tolar, J., Orchard, P. J., Bjoraker, K., Ziegler, R. S., Shapiro, E., & Charnas, L. R. (2007) · Bone Marrow Transplantation · doi:10.1038/sj.bmt.1705571 · Cited by 54 · cited 1× · see citing works
“transplant regiments, may be helpful as a means of increasing survival, particularly in patients with more advanced disease [54,55].”
BackgroundSelf-citationWakabayashi, T., Shimada, Y., Akiyama, K., Higuchi, T., Fukuda, T., Kobayashi, H., Eto, Y., Ida, H., & Ohashi, T. (2015) · Human Gene Therapy · doi:10.1089/hum.2014.158 · Cited by 53 · see citing works
Endocrine Dysfunction in X-Linked Adrenoleukodystrophy
Burtman, E., & Regelmann, M. O. (2016) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2016.01.003 · Cited by 50 · see citing works
Flavigny, E., Sanhaj, A., Aubourg, P. R., & Cartier, N. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00379-8 · Cited by 49 · cited 1× · see citing works
“Early studies with retroviral vectors suggested that this was feasible [66,67].”
BackgroundTreatment for Krabbe's disease: Finding the combination
Mikulka, C. R., & Sands, M. S. (2016) · Journal of Neuroscience Research · doi:10.1002/jnr.23822 · Cited by 48 · 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 · cited 1× · see citing works
“The pattern of white matter involvement is varied, but often the splenium is the area where changes are first observed, and in about 70% of the cases the cerebral disease is primarily located in the occipital area (Figure 1) [33,34].”
BackgroundLong-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 · cited 1× · see citing works
“There have been two subsequent reports regarding this study, which encompassed a total of 4 patients [72,73].”
ResultEvaluation of the risk of therapy-related MDS/AML after autologous stem cell transplantation
Gilliland, D. G., & Gribben, J. G. (2002) · Transplantation and Cellular Therapy · doi:10.1053/bbmt.2002.v8.pm11846355 · Cited by 44 · cited 1× · see citing works
“5 years) after autologous HSCT in patients who had received prior chemotherapy with alkylating agents and radiation [81,82].”
BackgroundFinke, J., Schmoor, C., Bertz, H., Marks, R., Wäsch, R., Zeiser, R., & Hackanson, B. W. (2016) · Bone Marrow Transplantation · doi:10.1038/bmt.2015.338 · Cited by 42 · cited 1× · see citing works
“The relapse-free survival in therapy-related MDS remains as low as 30–35% at 5 years [93,98].”
BackgroundAdrenoleukodystrophy: Failure of Immunosuppression to Prevent Neurological Progression
Stumpf, D. A. (1981) · Archives of Neurology · doi:10.1001/archneur.1981.00510010074014 · Cited by 41 · see citing works
Chiesa, R., Boelens, J. J., Duncan, C., Kühl, J., Sevin, C., Kapoor, N., Prasad, V. K., Lindemans, C. A., Jones, S. A., Amartino, H. M., et al. (2021) · Blood Advances · doi:10.1182/bloodadvances.2021005294 · Cited by 41 · see citing works
Self-citationRetroviral Transfer and Long-Term Expression of the Adrenoleukodystrophy Gene in Human CD34 + Cells
Doerflinger, N., Micléa, J.-M., Lopez, J., Chomienne, C., Bougneres, P. F., Aubourg, P. R., & Cartier, N. (1998) · Human Gene Therapy · doi:10.1089/hum.1998.9.7-1025 · Cited by 39 · see citing works
Clinical and radiographic course of arrested cerebral adrenoleukodystrophy
Mallack, E. J., van de Stadt, S. I. W., Caruso, P. A., Musolino, P. L., Sadjadi, R., Engelen, M., & Eichler, F. (2020) · Neurology · doi:10.1212/wnl.0000000000009626 · Cited by 39 · cited 1× · see citing works
“symptomatic cerebral disease die or progress to a vegetative state within several years [31].”
BackgroundTreatment of adrenoleukodystrophy with bone marrow transplantation
Malm, G., Ringdén, O. T. H., Anvret, M., von Döbeln, U., Hagenfeldt, L., Isberg, B., Knuutila, S., Nennesmo, I., Winiarski, J. H., & Marcus, C. (1997) · Acta Paediatrica · doi:10.1111/j.1651-2227.1997.tb08918.x · Cited by 37 · see citing works
Dietz, A. C., Duncan, C., Alter, B. P., Bresters, D., Cowan, M. J., Notarangelo, L. D., Rosenberg, P. S., Shenoy, S. S., Skinner, R., Walters, M. C., et al. (2016) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2016.10.004 · Cited by 36 · see citing works
Cognitive Evaluation of Neurologically Asymptomatic Boys With X-linked Adrenoleukodystrophy
Cox, C., Dubey, P., Raymond, G. V., Mahmood, A., Moser, A. B., & Moser, H. W. (2006) · Archives of Neurology · doi:10.1001/archneur.63.1.69 · Cited by 33 · see citing works
Self-citationAdrénoleucodystrophie liée à l'X
Aubourg, P. R. (2007) · Annales d Endocrinologie · doi:10.1016/j.ando.2007.04.002 · Cited by 32 · see citing works
Waldhüter, N., Köhler, W., Hemmati, P., Jehn, C. F., Peceny, R., Vuong, G. L., Arnold, R., & Kühl, J. (2019) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12044 · Cited by 31 · cited 1× · see citing works
“older patients, recent reports suggest adults with cerebral disease may have outcomes comparable to a pediatric age group [90,91].”
BackgroundUnterrainer, G. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.18.2609 · Cited by 30 · cited 1× · see citing works
“limited, and that increased expression of wild-type ALD protein can influence the relative amount in the membrane as opposed to a defective gene product [109].”
BackgroundClinical efficacy of haematopoietic stem cell transplantation for adult adrenoleukodystrophy
Matsukawa, T., Yamamoto, T., Honda, A., Toya, T., Ishiura, H., Mitsui, J., Tanaka, M., Hao, A., Shinohara, A., Ogura, M., et al. (2020) · Brain Communications · doi:10.1093/braincomms/fcz048 · Cited by 27 · cited 1× · see citing works
“older patients, recent reports suggest adults with cerebral disease may have outcomes comparable to a pediatric age group [90,91].”
BackgroundRole of family D ATP-binding cassette transporters (ABCD) in cancer
Hlaváč, V., & Souček, P. (2015) · Biochemical Society Transactions · doi:10.1042/bst20150114 · Cited by 26 · cited 1× · see citing works
“As mentioned, there has not been a described increase in the risk of malignancy in ALD patients, and there is not a clear role for ABCD1 in cancer [88].”
BackgroundConditions for combining gene therapy with bone marrow transplantation in murine Krabbe disease
Rafi, M. A., Luzi, P., & Wenger, D. A. (2020) · Bioimpacts · doi:10.34172/bi.2020.13 · Cited by 26 · see citing works
Petryk, A., Polgreen, L. E., Chahla, S., Miller, W., & Orchard, P. J. (2012) · Bone Marrow Transplantation · doi:10.1038/bmt.2012.33 · Cited by 25 · cited 1× · see citing works
“Interventions such as hematopoietic stem cell transplantation (HSCT) do not appear to modify the risk of developing AI or alter the pathology if it has already been established [24].”
BackgroundSelf-citationNewborn Screening and Emerging Therapies for X-Linked Adrenoleukodystrophy
Moser, A. B., & Fatemi, A. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2018.1585 · Cited by 22 · cited 1× · see citing works
“It correlates with clinical findings, as patients with symptomatic disease are likely to have a Loes score of 10 or higher [2].”
BackgroundNeurocognitive benchmarks following transplant for emerging cerebral adrenoleukodystrophy
Pierpont, E. I., Nascene, D. R., Shanley, R., Kenney-Jung, D. L., Ziegler, R. S., Miller, W. P., Gupta, A. O., Lund, T. C., Orchard, P. J., & Eisengart, J. B. (2020) · Neurology · doi:10.1212/wnl.0000000000009929 · Cited by 21 · cited 1× · see citing works
“who were identified to have ALD early in life and therefore able to receive treatment when cerebral lesions were quite small (MRI severity score < 5) [38].”
BackgroundSelf-citationNakano, T. A., Lau, B. W., Dickerson, K. E., Włodarski, M. W., Pollard, J. A., Shimamura, A., Hofmann, I., Sasa, G., Elghetany, T. M., Cada, M., et al. (2020) · Pediatric Blood & Cancer · doi:10.1002/pbc.28652 · Cited by 21 · see citing works
Post‐transplant adaptive function in childhood cerebral adrenoleukodystrophy
Pierpont, E. I., McCoy, E., King, K. E., Ziegler, R. S., Shanley, R., Nascene, D. R., Raymond, G. V., Phelan, R., Lund, T. C., Orchard, P. J., et al. (2018) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.526 · Cited by 16 · cited 2× · see citing works
“tive status at the time of HSCT predict independence after treatment [58].”
BackgroundSelf-citationQuality of life among boys with adrenoleukodystrophy following hematopoietic stem cell transplant
Beckmann, N. B., Miller, W. P., Dietrich, M. S., & Orchard, P. J. (2017) · Child Neuropsychology · doi:10.1080/09297049.2017.1380176 · Cited by 16 · cited 1× · see citing works
“with patients treated with less advanced disease [59].”
BackgroundSelf-citationCan early treatment of twitcher mice with high dose AAVrh10-GALC eliminate the need for BMT?
Rafi, M. A., Luzi, P., & Wenger, D. A. (2021) · Bioimpacts · doi:10.34172/bi.2021.21 · Cited by 15 · see citing works
Gupta, A. O., Nascene, D. R., Shanley, R., Kenney‐Jung, D. L., Eisengart, J. B., Lund, T. C., Orchard, P. J., & Pierpont, E. I. (2021) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12435 · Cited by 14 · see citing works
Self-citationGene therapy offers new hope for children with metachromatic leukodystrophy
Kurtzberg, J. (2022) · The Lancet · doi:10.1016/s0140-6736(22)00057-5 · Cited by 14 · see citing works
Andolina, J. R., Kletzel, M., Tse, W. T., Jacobsohn, D. A., Duerst, R. E., Schneiderman, J., Helenowski, I., RADEMAKER, A. W., & Chaudhury, S. (2011) · Pediatric Transplantation · doi:10.1111/j.1399-3046.2011.01479.x · Cited by 12 · cited 1× · see citing works
“The relapse-free survival in therapy-related MDS remains as low as 30–35% at 5 years [93,98].”
BackgroundYoo, J. W., Im, H. J., Kim, H., Koh, K., Kang, S. H., Min, S. Y., Choi, E. S., Jang, S., Park, C., & Seo, J. J. (2020) · Bone Marrow Transplantation · doi:10.1038/s41409-020-0814-8 · Cited by 12 · see citing works
Pediatric Myelodysplastic Syndromes
Patel, S. S. (2021) · Clinics in Laboratory Medicine · doi:10.1016/j.cll.2021.03.015 · Cited by 12 · see citing works
Ievers‐Landis, C. E., Brown, R. T., McCandless, S. E., & DEVINE, D. E. (1999) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/00004703-199902000-00005 · Cited by 8 · see citing works
Role for peroxisome proliferator-activated receptor-gamma in Alzheimer's disease.
van Geel (2001) · Open Repository and Bibliography (University of Luxembourg) · doi:10.1002/1531-8249(20010201)49:2 · Cited by 7 · see citing works
Self-citationÇiftçiler, R., Göker, H., Büyükaşık, Y., Topçu, M., Gevher, N., & Demiroğlu, H. (2019) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2019.06.019 · Cited by 6 · see citing works
Metabolic correction of fucosidosis fibroblasts by human α‐L‐fucosidase
Turner, B. M., Turner, V. S., & Hirschhorn, K. (1979) · Journal of Cellular Physiology · doi:10.1002/jcp.1040980124 · Cited by 5 · see citing works
Muranjan, M. N., Karande, S., Sankhe, S., & Eichler, S. (2018) · Journal of Postgraduate Medicine · doi:10.4103/jpgm.jpgm_349_17 · Cited by 5 · see citing works
Gene therapy for primary immunodeficiencies: up-to-date
Chetty, K., & Booth, C. (2020) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2021.1837108 · Cited by 4 · cited 2× · see citing works
“Unfortunately, the use of gene therapy in hematopoietic cell populations has previously been shown to be associated with a clear risk of hematologic malignancy [76].”
BackgroundMorita, M., Kaizawa, T., Yoda, T., Oyama, T., Asakura, R., Matsumoto, S., Nagai, Y., Watanabe, Y., Watanabe, S., Kobayashi, H., et al. (2020) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12346 · Cited by 3 · cited 1× · see citing works
“cells showed engraftment of bone marrow-derived microglialike cells in the brain but failed to show a decrease in VLCFA accumulation in the cerebrum [65].”
BackgroundOrchard, P. J., Duncan, C., Eichler, F., Oliveira, S. N. D., Thrasher, A. J., Sevin, C., Amartino, H. M., Smith, N. J. C., Kühl, J., Kenney‐Jung, D. L., et al. (2021) · Transplantation and Cellular Therapy · doi:10.1016/s2666-6367(21)00149-4 · Cited by 2 · see citing works
Self-citationIncreased activity of surviving locus ceruleus neurons in Alzheimer's disease
Moser (1999) · Pure Amsterdam UMC · doi:10.1002/1531-8249(199901)45:1
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Kwiatkowski, J. L., Walters, M. C., Hongeng, S., Yannaki, E., Kulozik, A. E., Kunz, J. B., Sauer, M. G., Thrasher, A. J., Thuret, I., Lal, A., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01884-1 · Cited by 53 · see citing works
X-linked adrenoleukodystrophy and primary adrenal insufficiency
Cappa, M., Todisco, T., & Bizzarri, C. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1309053 · Cited by 28 · see citing works
Bzhilyanskaya, V., Ma, L., Liu, S., Fox, L. R., Whittaker, M. N., Meis, R. J., Choi, U., Lawson, A., Ma, M., Theobald, N., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adj6779 · Cited by 27 · see citing works
VUS: Variant of uncertain significance or very unclear situation?
Kemp, S., Orsini, J. J., Ebberink, M. S., Engelen, M., & Lund, T. C. (2023) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2023.107678 · Cited by 25 · see citing works
Self-citationNewborn screening for adrenoleukodystrophy: International experiences and challenges
Videbæk, C. S., Melgaard, L., Lund, A. M., & Grønborg, S. W. (2023) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2023.107734 · Cited by 25 · see citing works
Current Advances and Challenges in Gene Therapies for Neurologic Disorders
Porcari, G. S., Collyer, J. W., Adang, L. A., & Rajan, D. S. (2025) · Neurology Genetics · doi:10.1212/nxg.0000000000200229 · Cited by 23 · see citing works
“35 In addition to carefully weighing bene fi ts, risks, and treatment timing, the current recommended monitoring includes complete blood counts with di ff erential every 6 months after treatment for at least 15 years with the addition of integration site analysis or other dedicated clonal expansion…”
Gupta, A. O., Azul, M., Bhoopalan, S., Abraham, A., Bertaina, A., Bidgoli, A., Bonfim, C., DeZern, A. E., Li, J., Louis, C., et al. (2024) · Cytotherapy · doi:10.1016/j.jcyt.2024.06.002 · Cited by 15 · see citing works
Self-citationGene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.
Metovic, J., Li, Y., Gong, Y., & Eichler, F. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00443 · Cited by 16 · see citing works
“As of spring 2024, seven cases of myelodysplastic syndrome or acute myelogenous leukemia have been reported among more than 70 boys with childhood CALD treated with eli-cel to date [28,206].”
BackgroundBouziana, S., & Bouzianas, D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179518 · Cited by 15 · see citing works
“…adrenoleukodystrophy, the top abundant integration sites of SIN LVs were genes involved in cell cycle regulation, cell division and oncogenesis; such genes included SGM6, CCND2 and MECOM, leading to clonal expansion and subsequent reports of MDS cases related to the viral insertion [67,68].”
BackgroundRare forms of genetic paediatric adrenal insufficiency: Excluding congenital adrenal hyperplasia
Hasenmajer, V., Ferrigno, R., Minnetti, M., Pellegrini, B., Isidori, A. M., Lenzi, A., Salerno, M., Cappa, M., Chan, L. F., Martino, M. C. D., et al. (2023) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09784-7 · Cited by 13 · see citing works
Gene and Cellular Therapies for Leukodystrophies
Aerts‐Kaya, F., & van Til, N. P. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15112522 · Cited by 13 · see citing works
Pierpont, E. I., Isaia, A., McCoy, E., Brown, S. J., Gupta, A. O., & Eisengart, J. B. (2022) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12581 · Cited by 11 · see citing works
“, gene therapy) hold promise to continue to improve the outlook for patients with cerebral ALD.(17) These major advances have enabled a shift in focus from methods to keep patients alive and prevent neurological devastation toward goals such as maximizing neurocognitive function, mental health and quality of life.”
BackgroundSelf-citationZuo, X., & Chen, Z. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02361-0 · Cited by 12 · see citing works
“However, when patients fail to engraft donor-derived cells after transplantation, they typically exhibit a return of neuroinflammation and further deterioration of white matter [56].”
BackgroundGarcía‐Cazorla, À., Sevin, C., Ribeiro‐Constante, J., Yazbeck, E., Rosewich, H., Jimenez, S., Chiang, G. C.-Y., Rapalino, O., Caruso, P. A., Balentine, D., et al. (2025) · EClinicalMedicine · doi:10.1016/j.eclinm.2025.103265 · Cited by 9 · see citing works
“25,26 Therefore, there is a signi fi cant unmet need for globally accessible, lower-risk therapies that can be administered immediately upon cerebral lesion detection.”
John, T. D., Marón, G. M., Abraham, A., Bertaina, A., Bhoopalan, S. V., Bidgoli, A., Bonfim, C., Coleman, Z., Dezern, A. E., Li, J., et al. (2024) · Cytotherapy · doi:10.1016/j.jcyt.2024.02.005 · Cited by 7 · see citing works
Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy
Onuki, T., Tajika, M., Sugiyama, Y., Shimura, M., Ichimoto, K., Tanaka, T., Nyuzuki, H., Kosuga, M., Migita, O., Ito, T., et al. (2025) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-025-03848-4 · Cited by 6 · see citing works
“The most severe form of ALD, the pediatric cerebral type, is a progressive disease that begins at mean 7.1 years of age and is characterized by behavioral abnormalities, vision and hearing loss, gait disturbance, and neurodevelopmental regression [2].”
InfluentialTucci, F., Consiglieri, G., Cossutta, M., & Bernardo, M. E. (2023) · HemaSphere · doi:10.1097/hs9.0000000000000953 · Cited by 6 · see citing works
Li, C., Terluk, M. R., & Kartha, R. V. (2025) · British Journal of Pharmacology · doi:10.1111/bph.70044 · Cited by 6 · see citing works
“Furthermore, allogeneic transplantation is typically accompanied by significant complications and carries a risk of infections, while gene therapy poses the potential risk of inducing hematologic malignancy (Gupta et al., 2022).”
Stem cell and gene therapies for leukodystrophies
Lin, W., Zhang, M., Zheng, S., & Lian, Q. (2025) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2025.101527 · Cited by 6 · see citing works
“82 Critical unmet needs include (1) global standardization of newborn screening to enable early intervention, (2) antileukemia interventions need to be considered, (3) vector engineering to improve CNS-targeted delivery, and (4) cost-reduction strategies for scalable HSC-GT manufacturing.”
Wang, Q., Wang, J., Ling, Z., Cui, Z., Gong, J., Zhang, R., Li, S., Wang, Y., Yang, R., Huang, D., et al. (2024) · 中国科学通报：英文版 · doi:10.1016/j.scib.2024.04.072 · Cited by 5 · see citing works
Diffusion Tensor Imaging in Boys With Adrenoleukodystrophy
Pierpont, E. I., Labounek, R., Gupta, A. O., Lund, T. C., Orchard, P. J., Dobyns, W. B., Bondy, M. T., Paulson, A. L., Metz, A., Shanley, R., et al. (2024) · Neurology · doi:10.1212/wnl.0000000000209764 · Cited by 5 · see citing works
“4-6 However, HCT must be performed at an early stage to preserve neurocognitive function 7 The severity of cerebral lesions is conventionally assessed using the radiologic scoring system developed by Loes, which tallies the number and extent of brain structures a ff ected by lesions on anatomical .”
MethodSelf-citationVidebæk, C. S., Grønborg, S. W., Lund, A. M., & Olesen, M. L. (2024) · International Journal of Neonatal Screening · doi:10.3390/ijns10040073 · Cited by 5 · see citing works
The promise of in vivo HSC prime editing
Sweeney, C. L., & Ravin, S. S. D. (2023) · Blood · doi:10.1182/blood.2023019922 · Cited by 5 · see citing works
Videbæk, C. S., Dunø, M., Lindquist, S. G., Larsen, V. A., Kjær, M. W., Melgaard, L., Nielsen, J. E., Grønborg, S. W., & Lund, A. M. (2025) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2025.109265 · Cited by 4 · see citing works
Easily misdiagnosed X-linked adrenoleukodystrophy
Wang, Q., Wang, Y., Wang, J., Liu, L.-Y., Gao, J., Hao, G.-Z., Chen, C., Lü, Q., Dun, S., Zhang, Q., et al. (2024) · The Italian Journal of Pediatrics/Italian journal of pediatrics · doi:10.1186/s13052-024-01669-y · Cited by 4 · see citing works
“Eventually, patients may develop major functional dysfunction (MFD), such as being bedridden, blind, unable to speak or respond, fed by gastrostomy; moreover, death usually occurs two to four years after onset of symptoms [29].”
BackgroundGene therapy for neurodegenerative disorders in children: dreams and realities
Boespflug‐Tanguy, O., Sevin, C., & Piguet, F. (2023) · Archives de Pédiatrie · doi:10.1016/s0929-693x(23)00225-7 · Cited by 4 · see citing works
Hematopoietic stem cell gene therapy of neurometabolic lysosomal storage diseases
Consiglieri, G., Tucci, F., & Bernardo, M. E. (2025) · Brain and Development · doi:10.1016/j.braindev.2025.104384 · Cited by 3 · see citing works
C26:0-lysophosphatidylcholine in X-linked adrenoleukodystrophy
Jaspers, Y. R. J., Dijkstra, I. M. E., Engelen, M., & Kemp, S. (2026) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2026.109070 · Cited by 3 · see citing works
Self-citationProgress in leukodystrophies with zebrafish
Shih, H., Raas, Q., & Bonkowsky, J. L. (2024) · Development Growth & Differentiation · doi:10.1111/dgd.12907 · Cited by 3 · see citing works
“Multiple approved treatments exist and clinical trials are ongoing (Dulski et al., 2022; Gupta et al., 2022; Messina & Gissen, 2023; Vanderver et al., 2020).”
BackgroundAccelerated Course of Cerebral Adrenoleukodystrophy After Coronavirus Disease 2019 Infection
Wang, Q., Wang, J., Wang, Y., He, W., Chen, F., Gao, J., Lu, Q., Wang, Y., Dun, S., Zhang, Q., et al. (2024) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2023.12.021 · Cited by 3 · see citing works
Development of a rabbit model for adrenoleukodystrophy: A pilot study on gene therapy using rAAV9
Zhou, X., Ma, C.-Y., Zhang, X., Xu, X., Duan, F., Kou, M., Liu, H., Zeng, L., Guo, L., Chen, S., et al. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102469 · Cited by 3 · see citing works
Chaudhary, R., Rehman, M., Agarwal, V., Kumar, A., Kaushik, A. S., Srivastava, S., Srivastava, S., Verma, R., Rajinikanth, P. S., & Mishra, V. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122953 · Cited by 2 · see citing works
Wang, Y., Liu, D., Gao, H., Liu, W., & Mao, Y. (2025) · Journal of Pediatric Hematology/Oncology · doi:10.1097/mph.0000000000003069 · Cited by 2 · see citing works
Gene Therapy–Related Malignancy and the Risk of Cancer Exceptionalism
Benedetti, D. J., Marron, J. M., & Kodish, E. D. (2026) · Journal of Clinical Oncology · doi:10.1200/jco-25-01844 · Cited by 2 · see citing works
Nervonic acid supplementation mitigates disease severity biomarkers in adrenoleukodystrophy
Li, C., Braaten, K., Moser, A. B., Fallatah, W., Lorentson, M., Huguenin, S. M., Torrey, A. C., Terluk, M. R., Durose, W., Nolan, E. E., et al. (2026) · Neurotherapeutics · doi:10.1016/j.neurot.2026.e00890 · Cited by 3 · see citing works
“Current treatment options, including allogeneic hematopoietic stem cell transplantation and lentiviral gene therapy, are limited to early-stage cALD and carry substantial risks, such as graft failure, graft-versus-host disease, transplant-related mortality, and insertional oncogenesis [10 – 12].”
Self-citationSeizures in childhood cerebral adrenoleukodystrophy
Page, N., Nagy, A. M., Eichler, F., & Ream, M. A. (2025) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.16321 · Cited by 2 · see citing works
Bethin, K. E., Majumdar, I., & Muglia, L. J. (2024) · Springer eBooks · doi:10.1007/978-3-031-66296-6_10 · Cited by 2 · see citing works
Rajakumar, H. K., Sathyabal, V. C., Nachiappan, R., & Vijayaramanujam, S. K. (2024) · Degenerative Neurological and Neuromuscular Disease · doi:10.2147/dnnd.s442985 · Cited by 1 · see citing works
Izmailov, A., Minyazeva, I., Аршалуйсович, М. В., Safiullov, Z. Z., Gazizov, I. M., Salafutdinov, I. I., Markelova, M., Garifulin, R. R., Шмаров, М. М., Logunov, D. Y., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12112568 · Cited by 1 · see citing works
“In cell-mediated (ex vivo) gene therapy, retroviruses expressing the ADA gene are used for treating severe combined immunodeficiency (SCID) [17], and lentiviruses are utilized to deliver the ABCD1 gene for the treatment of adrenoleukodystrophy (ALD) [18].”
Martens, R. C., Broulíková, H. M., Engelen, M., Kemp, S., Boelen, A., de Jonge, R., Bosmans, J. E., & Heijboer, A. C. (2025) · International Journal of Neonatal Screening · doi:10.3390/ijns11030053 · Cited by 1 · see citing works
“Progression can be halted by allogeneic hematopoietic stem cell transplantation (HSCT), but the outcome is only favourable in those patients that are treated in the asymptomatic stage (i.e. leukodystrophy on MRI in an early stage without symptoms) [4,10–14].”
Self-citationNeurofilament light chain as a prognostic marker in cerebral adrenoleukodystrophy
Pierpont, E. I., Gupta, A. O., Eisengart, J. B., Shanley, R., Evans, R. O., Loes, D. J., Nascene, D. R., Narayanan, S., Orchard, P. J., & Lund, T. C. (2025) · Brain · doi:10.1093/brain/awaf359 · Cited by 1 · see citing works
“18,19 Identification of additional reliable, objective metrics that can assist with predicting functional outcomes after treatment therefore offers potential to contribute to optimizing disease management.”
Self-citationMansouri, M., Smol, T., Louhabe, N., Rama, M., Rada, N., Fdil, N., Bouskraoui, M., & Aboussair, N. (2025) · Balkan Journal of Medical Genetics · doi:10.2478/bjmg-2025-0002 · Cited by 1 · see citing works
“However, boys whose neurological disease has progressed too far at the time of diagnosis are not eligible for this targeted therapy [16].”
Safety and efficacy analysis of in vivo lentiviral gene therapy in pre-clinical ARC syndrome models
Cozmescu, A. C., Nazari, M., Touramanidou, L., Gurung, S., Perocheau, D. P. B., Sebire, N. J., Hu, Y., Goldsworthy, S., Burden, J. J., Khalil, Y., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-73631-x · Cited by 1 · see citing works
“However, recent clinical research fi ndings raised concerns about the possible oncogenic events, with a signi fi cant number of cases of myelodysplastic syndrome linked to the internal MNDU3 promoter used in the vector design 26 .”
Ogata, J., Shimada, Y., Ohashi, T., & Kobayashi, H. (2024) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2024.108494 · Cited by 1 · see citing works
Adrenoleukodystrophy Presenting as Gait Disturbance in a Girl Child
Balhara, K., Singla, N., Agarwal, P., Bedi, N., & Abrol, P. (2023) · Indian Journal of Health Sciences and Care · doi:10.5958/2394-2800.2023.00018.5 · Cited by 1 · see citing works
Gene Therapy in Neurological Diseases
Aluçlu, M. U. (2024) · doi:10.69860/nobel.9786053358824.6 · Cited by 1 · see citing works
Therapie der X-chromosomalen Adrenoleukodystrophie
Köhler, W. (2024) · DGNeurologie · doi:10.1007/s42451-024-00645-4
Kwiatkowski, J. L., Walters, M. C., Hongeng, S., Yannaki, E., Kulozik, A. E., Kunz, J. B., Sauer, M. G., Thrasher, A. J., Thuret, I., Lal, A., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4805812
Childhood-onset leukodystrophy
Federico, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-99417-0.00001-x
Dimitrov, M., Ebens, C. L., & Tolar, J. (2024) · British Journal of Dermatology · doi:10.1093/bjd/ljae332
Raymond, G. V. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-19041-4.00061-3
Self-citationX-linked adrenoleukodystrophy/adrenomyeloneuropathy
Rizzo, W. B., & Baker, C. V. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00109-6
Raymond, G. V., Baranano, K. W., Wangler, M. F., & Fatemi, A. S. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-10944-7.00065-2
Self-citationSy, J. A. C., Tan, P. L., Lin, J. B., Tay, S. K. H., & Chin, H.-L. L. (2025) · Frontiers in Pediatrics · doi:10.3389/fped.2025.1650645
“Furthermore, lentiviral gene therapy using autologous stem cells is also emerging as an alternative strategy for treating cALD (4).”
Reshmi, R., & Kaur, D. (2025) · Egyptian Journal of Medical Human Genetics · doi:10.1186/s43042-025-00773-w
“The prevalence of ALD is estimated as 1 in 14,000– 17,000 male births [27].”
Tang, C.-J., Tan, M., Cai, Y., Liu, S., Xie, T., Jiang, X., Tao, L., Huang, Y., & Tang, F. (2025) · International Journal of Neonatal Screening · doi:10.3390/ijns11030071
“Hematopoietic stem cell transplantation has been confirmed as an effective treatment to halt cerebral demyelination and prevent death due to CALD in the early stages of the disease [2].”
X-linked adrenoleukodystrophy: literature review, description of clinical cases
Alekseeva, V. A., Gavrichenko, A. V., Yakovlev, A. A., Sokolova, M. G., Barantsevich, E. R., & Abramova, A. P. (2025) · The Scientific Notes of the Pavlov University · doi:10.24884/1607-4181-2025-32-2-100-112
Recognizing Cerebral Pathology in Adrenoleukodystrophy Amid the Noise
Pierpont, E. I. (2025) · Neurology · doi:10.1212/wnl.0000000000214394
Self-citationInborn errors of metabolism and osteopetrosis
Fernandes, J. F., Rodrigues, A. M., Daudt, L. E., Klinger, P. H. D. S., & Bonfim, C. (2025) · JOURNAL OF BONE MARROW TRANSPLANTATION AND CELLULAR THERAPY · doi:10.46765/2675-374x.2025v6n1e297
“There is not known association between genotype and phenotype 15,16 .”
InfluentialAdditional file 1 of Easily misdiagnosed X-linked adrenoleukodystrophy
Wang, Q.-H., Wang, Y.-Y., Wang, J., Liu, L.-Y., Gao, J., Hao, G.-Z., Chen, C., Lu, Q., Dun, S., Zhang, Q., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26157086
Pretreatment blood NfL indicates response to cellular therapies in cerebral adrenoleukodystrophy
Weinhofer, I., Ponleitner, M., Rommer, P. S., Bergner, C. G., Starke, S., Gräfe, D., Merkenschlager, A., Forss‐Petter, S., Köhler, W., Berger, J., et al. (2026) · Communications Medicine · doi:10.1038/s43856-026-01525-6
National Trends in MRI Screening and Transplant for US Adult Men With X-Linked Adrenoleukodystrophy
Alton, W. Y., & Bonkowsky, J. L. (2026) · Neurology Open Access · doi:10.1212/wn9.0000000000000096
Zaher, E., Shapira-Rootman, M., Tal, G., Ravid, S., Meirson, H., Zerem, A., & Duvdevan, N. (2026) · Journal of Neuro-Ophthalmology · doi:10.1097/wno.0000000000002482
Gene therapy in leukodystrophies
Vafadar, A., Heidari, Z., & Savardashtaki, A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-40467-2.00010-5
Furuta, Y., Li, H., Keller, S. R., Phillips, J. A., Tinker, R. J., Asano, E., & Juhász, C. (2026) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.70313
Newborn Screening for X-Linked Adrenoleukodystrophy: A Systematic Literature Review
Cabrera-González, M. I., de Diego‐Otero, Y., & Yahyaoui, R. (2026) · International Journal of Neonatal Screening · doi:10.3390/ijns12040080
“In addition to HSCT, other emerging therapies, including lentiviral gene therapy, have shown promising results although their availability and regulatory status vary across regions [5,13].”
- Authors
- Gupta, A. O., Raymond, G., Pierpont, E. I., Kemp, S., McIvor, R. S., Rayannavar, A., Miller, B., Lund, T. C., & Orchard, P. J.
- Affiliations
- University of Minnesota (US)
- Kennedy Krieger Institute (US)
- Amsterdam Neuroscience (NL)
- Corresponding author
- Orchard, Paul J
- ORCID
- Venue
- Expert Opinion on Biological Therapy
- Publisher
- Informa UK Limited
- Published
- 2022-09-02
- Volume
- 22
- Issue
- 9
- Pages
- 1151-1162
- ISSN
- 1471-2598 (ISSN-L)
- 1744-7682
- OpenAlex
- W4295901830
- Cited by
- 67
- References
- 109
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 27 · 2023: 10 · 2022: 1
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Expert Opinion on Biological Therapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- cerebral adrenoleukodystrophy, allogeneic hematopoietic stem cell transplantation, lentiviral gene therapy, ABCA1 gene, early treatment, disease progression, neuroinflammation, gene therapy clinical trials
- MeSH terms
- Adrenoleukodystrophy, Adult, Humans, Male, Transplantation, Homologous, Genetic Therapy, Hematopoietic Stem Cell Transplantation
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
