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Erschienen in: Wiener Medizinische Wochenschrift 9-10/2017

10.05.2017 | main topic

Therapeutic strategies in adrenoleukodystrophy

verfasst von: Bela R. Turk, Ann B. Moser, Ali Fatemi

Erschienen in: Wiener Medizinische Wochenschrift | Ausgabe 9-10/2017

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Summary

Adrenoleukodystrophy (ALD) is an X‑linked hereditary disorder due to mutations of the ABCD1 gene, which encodes a peroxisomal transport protein necessary for very long-chain fatty acid degradation (VLCFA). Toxic accumulation thereof is associated with a proinflammatory state and eventual cell death in multiple tissues. ALD may manifest either as a fatal, rapidly progressive demyelinating disease in boys and adult men, or as a slowly progressive adult-onset long-tract myelopathy along with peripheral neuropathy. Our understanding of manifold mechanisms implicated in the disease pathology is currently incomplete, as neither genotype–phenotype correlation nor the trigger for cerebral disease has been described. Therapy objectives are therefore broadly aimed at correcting either the gene mutation or downstream molecular effects, such as oxidative stress. Advancements in disease detection, including the newly implemented newborn screening in the US and imaging modalities, allow for more timely intervention in the form of hematopoietic stem cell transplantation (HSCT), which may only be performed in early cerebral disease states.
Literatur
1.
Zurück zum Zitat Aubourg P, Adamsbaum C, Lavallard-Rousseau MC, Rocchiccioli F, Cartier N, Jambaqué I, et al. A two-year trial of oleic and erucic acids (“Lorenzo’s oil”) as treatment for adrenomyeloneuropathy. New Engl J Med. 1993;329(11):745–52. doi:10.1056/NEJM199309093291101.CrossRefPubMed Aubourg P, Adamsbaum C, Lavallard-Rousseau MC, Rocchiccioli F, Cartier N, Jambaqué I, et al. A two-year trial of oleic and erucic acids (“Lorenzo’s oil”) as treatment for adrenomyeloneuropathy. New Engl J Med. 1993;329(11):745–52. doi:10.​1056/​NEJM199309093291​101.CrossRefPubMed
2.
Zurück zum Zitat Baumann M, Korenke GC, Weddige-Diedrichs A, Wilichowski E, Hunneman DH, Wilken B, et al. Haematopoietic stem cell transplantation in 12 patients with cerebral X‑linked adrenoleukodystrophy. Eur J Pediatr. 2003;162(1):6–14. doi:10.1007/s00431-002-1097-3.CrossRefPubMed Baumann M, Korenke GC, Weddige-Diedrichs A, Wilichowski E, Hunneman DH, Wilken B, et al. Haematopoietic stem cell transplantation in 12 patients with cerebral X‑linked adrenoleukodystrophy. Eur J Pediatr. 2003;162(1):6–14. doi:10.​1007/​s00431-002-1097-3.CrossRefPubMed
4.
Zurück zum Zitat Bezman L, Moser AB, Raymond GV, Rinaldo P, Watkins PA, Smith KD, et al. Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screening. Ann Neurol. 2001;49(4):512–7.CrossRefPubMed Bezman L, Moser AB, Raymond GV, Rinaldo P, Watkins PA, Smith KD, et al. Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screening. Ann Neurol. 2001;49(4):512–7.CrossRefPubMed
6.
Zurück zum Zitat Birken DL, Oldendorf WH. N‑acetyl-L-aspartic acid: a literature review of a compound prominent in 1 H-NMR spectroscopic studies of brain. Neurosci Biobehav Rev. 1989;13(1):23–31.CrossRefPubMed Birken DL, Oldendorf WH. N‑acetyl-L-aspartic acid: a literature review of a compound prominent in 1 H-NMR spectroscopic studies of brain. Neurosci Biobehav Rev. 1989;13(1):23–31.CrossRefPubMed
7.
Zurück zum Zitat Cartier N, Hacein-Bey-Abina S, Bartholomae CC, Veres G, Schmidt M, Kutschera I, et al. Hematopoietic stem cell gene therapy with a lentiviral vector in X‑linked adrenoleukodystrophy. Science. 2009;326(5954):818–23. doi:10.1126/science.1171242.CrossRefPubMed Cartier N, Hacein-Bey-Abina S, Bartholomae CC, Veres G, Schmidt M, Kutschera I, et al. Hematopoietic stem cell gene therapy with a lentiviral vector in X‑linked adrenoleukodystrophy. Science. 2009;326(5954):818–23. doi:10.​1126/​science.​1171242.CrossRefPubMed
10.
Zurück zum Zitat Dubey P, Fatemi A, Huang H, Nagae-Poetscher L, Wakana S, Barker PB, et al. Diffusion tensor-based imaging reveals occult abnormalities in adrenomyeloneuropathy. Ann Neurol. 2005b;58(5):758–66. doi:10.1002/ana.20643.CrossRefPubMed Dubey P, Fatemi A, Huang H, Nagae-Poetscher L, Wakana S, Barker PB, et al. Diffusion tensor-based imaging reveals occult abnormalities in adrenomyeloneuropathy. Ann Neurol. 2005b;58(5):758–66. doi:10.​1002/​ana.​20643.CrossRefPubMed
11.
Zurück zum Zitat Eichler FS, Itoh R, Barker PB, Mori S, Garrett ES, van Zijl PCM, et al. Proton MR spectroscopic and diffusion tensor brain MR imaging in X‑linked adrenoleukodystrophy: initial experience. Radiology. 2002;225(1):245–52. doi:10.1148/radiol.2251011040.CrossRefPubMed Eichler FS, Itoh R, Barker PB, Mori S, Garrett ES, van Zijl PCM, et al. Proton MR spectroscopic and diffusion tensor brain MR imaging in X‑linked adrenoleukodystrophy: initial experience. Radiology. 2002;225(1):245–52. doi:10.​1148/​radiol.​2251011040.CrossRefPubMed
12.
Zurück zum Zitat Eichler FS, Ren J‑Q, Cossoy M, Rietsch AM, Nagpal S, Moser AB, et al. Is microglial apoptosis an early pathogenic change in cerebral X‑linked adrenoleukodystrophy? Ann Neurol. 2008;63(6):729–42. doi:10.1002/ana.21391.CrossRefPubMed Eichler FS, Ren J‑Q, Cossoy M, Rietsch AM, Nagpal S, Moser AB, et al. Is microglial apoptosis an early pathogenic change in cerebral X‑linked adrenoleukodystrophy? Ann Neurol. 2008;63(6):729–42. doi:10.​1002/​ana.​21391.CrossRefPubMed
13.
15.
Zurück zum Zitat Fatemi A, Barker PB, Ulug AM, Nagae-Poetscher LM, Beauchamp NJ, Moser AB, et al. MRI and proton MRSI in women heterozygous for X‑linked adrenoleukodystrophy. Neurology. 2003;60(8):1301–7.CrossRefPubMed Fatemi A, Barker PB, Ulug AM, Nagae-Poetscher LM, Beauchamp NJ, Moser AB, et al. MRI and proton MRSI in women heterozygous for X‑linked adrenoleukodystrophy. Neurology. 2003;60(8):1301–7.CrossRefPubMed
17.
Zurück zum Zitat Fourcade S, Lopez-Erauskin J, Galino J, Duval C, Naudi A, Jove M, et al. Early oxidative damage underlying neurodegeneration in X‑adrenoleukodystrophy. Hum Mol Genet. 2008;17(12):1762–73. doi:10.1093/hmg/ddn085.CrossRefPubMed Fourcade S, Lopez-Erauskin J, Galino J, Duval C, Naudi A, Jove M, et al. Early oxidative damage underlying neurodegeneration in X‑adrenoleukodystrophy. Hum Mol Genet. 2008;17(12):1762–73. doi:10.​1093/​hmg/​ddn085.CrossRefPubMed
18.
Zurück zum Zitat Garside S, Rosebush PI, Levinson AJ, Mazurek MF. Late-onset adrenoleukodystrophy associated with long-standing psychiatric symptoms. J Clin Psychiatry. 1999;60(7):460–8.CrossRefPubMed Garside S, Rosebush PI, Levinson AJ, Mazurek MF. Late-onset adrenoleukodystrophy associated with long-standing psychiatric symptoms. J Clin Psychiatry. 1999;60(7):460–8.CrossRefPubMed
21.
Zurück zum Zitat Hoefnagel D, Brun A, Ingbar SH, Goldman H. Addison’s disease and diffuse cerebral sclerosis. J Neurol Neurosurg Psychiatr. 1967;30(1):56–60.CrossRefPubMedCentral Hoefnagel D, Brun A, Ingbar SH, Goldman H. Addison’s disease and diffuse cerebral sclerosis. J Neurol Neurosurg Psychiatr. 1967;30(1):56–60.CrossRefPubMedCentral
22.
Zurück zum Zitat Igarashi M, Schaumburg HH, Powers J, Kishmoto Y, Kolodny E, Suzuki K. Fatty acid abnormality in adrenoleukodystrophy. J Neurochem. 1976;26(4):851–60.CrossRefPubMed Igarashi M, Schaumburg HH, Powers J, Kishmoto Y, Kolodny E, Suzuki K. Fatty acid abnormality in adrenoleukodystrophy. J Neurochem. 1976;26(4):851–60.CrossRefPubMed
24.
Zurück zum Zitat Korenke GC, Fuchs S, Krasemann E, Doerr HG, Wilichowski E, Hunneman DH, Hanefeld F. Cerebral adrenoleukodystrophy (ALD) in only one of monozygotic twins with an identical ALD genotype. Ann Neurol. 1996;40(2):254–7. doi:10.1002/ana.410400221.CrossRefPubMed Korenke GC, Fuchs S, Krasemann E, Doerr HG, Wilichowski E, Hunneman DH, Hanefeld F. Cerebral adrenoleukodystrophy (ALD) in only one of monozygotic twins with an identical ALD genotype. Ann Neurol. 1996;40(2):254–7. doi:10.​1002/​ana.​410400221.CrossRefPubMed
25.
Zurück zum Zitat Kumar AJ, Köhler W, Kruse B, Naidu S, Bergin A, Edwin D, Moser HW. MR findings in adult-onset adrenoleukodystrophy. Am J Neuroradiol. 1995;16(6):1227–37.PubMed Kumar AJ, Köhler W, Kruse B, Naidu S, Bergin A, Edwin D, Moser HW. MR findings in adult-onset adrenoleukodystrophy. Am J Neuroradiol. 1995;16(6):1227–37.PubMed
26.
Zurück zum Zitat Laureti S, Casucci G, Santeusanio F, Angeletti G, Aubourg P, Brunetti P. X‑linked adrenoleukodystrophy is a frequent cause of idiopathic Addison’s disease in young adult male patients. J Clin Endocrinol Metab. 1996;81(2):470–4. doi:10.1210/jcem.81.2.8636252.PubMed Laureti S, Casucci G, Santeusanio F, Angeletti G, Aubourg P, Brunetti P. X‑linked adrenoleukodystrophy is a frequent cause of idiopathic Addison’s disease in young adult male patients. J Clin Endocrinol Metab. 1996;81(2):470–4. doi:10.​1210/​jcem.​81.​2.​8636252.PubMed
27.
Zurück zum Zitat Loes DJ, Hite S, Moser H, Stillman AE, Shapiro E, Lockman L, et al. Adrenoleukodystrophy: a scoring method for brain MR observations. Am J Neuroradiol. 1994;15(9):1761–6.PubMed Loes DJ, Hite S, Moser H, Stillman AE, Shapiro E, Lockman L, et al. Adrenoleukodystrophy: a scoring method for brain MR observations. Am J Neuroradiol. 1994;15(9):1761–6.PubMed
28.
Zurück zum Zitat Loes DJ, Fatemi A, Melhem ER, Gupte N, Bezman L, Moser HW, Raymond GV. Analysis of MRI patterns aids prediction of progression in X‑linked adrenoleukodystrophy. Neurology. 2003;61(3):369–74.CrossRefPubMed Loes DJ, Fatemi A, Melhem ER, Gupte N, Bezman L, Moser HW, Raymond GV. Analysis of MRI patterns aids prediction of progression in X‑linked adrenoleukodystrophy. Neurology. 2003;61(3):369–74.CrossRefPubMed
30.
Zurück zum Zitat Mahmood A, Raymond GV, Dubey P, Peters C, Moser HW. Survival analysis of haematopoietic cell transplantation for childhood cerebral X‑linked adrenoleukodystrophy: a comparison study. Lancet Neurol. 2007;6(8):687–92. doi:10.1016/S1474-4422(07)70177-1.CrossRefPubMed Mahmood A, Raymond GV, Dubey P, Peters C, Moser HW. Survival analysis of haematopoietic cell transplantation for childhood cerebral X‑linked adrenoleukodystrophy: a comparison study. Lancet Neurol. 2007;6(8):687–92. doi:10.​1016/​S1474-4422(07)70177-1.CrossRefPubMed
31.
Zurück zum Zitat Melhem ER, Loes DJ, Georgiades CS, Raymond GV, Moser HW. X‑linked adrenoleukodystrophy: the role of contrast-enhanced MR imaging in predicting disease progression. Am J Neuroradiol. 2000;21(5):839–44.PubMed Melhem ER, Loes DJ, Georgiades CS, Raymond GV, Moser HW. X‑linked adrenoleukodystrophy: the role of contrast-enhanced MR imaging in predicting disease progression. Am J Neuroradiol. 2000;21(5):839–44.PubMed
32.
Zurück zum Zitat Miller WP, Rothman SM, Nascene D, Kivisto T, DeFor TE, Ziegler RS, et al. Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood. 2011;118(7):1971–8. doi:10.1182/blood-2011-01-329235.CrossRefPubMed Miller WP, Rothman SM, Nascene D, Kivisto T, DeFor TE, Ziegler RS, et al. Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood. 2011;118(7):1971–8. doi:10.​1182/​blood-2011-01-329235.CrossRefPubMed
35.
Zurück zum Zitat Mosser J, Douar AM, Sarde CO, Kioschis P, Feil R, Moser H, et al. Putative X‑linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature. 1993;361(6414):726–30. doi:10.1038/361726a0.CrossRefPubMed Mosser J, Douar AM, Sarde CO, Kioschis P, Feil R, Moser H, et al. Putative X‑linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature. 1993;361(6414):726–30. doi:10.​1038/​361726a0.CrossRefPubMed
37.
Zurück zum Zitat O’Neill BP, Moser HW, Saxena KM, Marmion LC. Adrenoleukodystrophy: clinical and biochemical manifestations in carriers. Neurology. 1984;34(6):798–801.CrossRefPubMed O’Neill BP, Moser HW, Saxena KM, Marmion LC. Adrenoleukodystrophy: clinical and biochemical manifestations in carriers. Neurology. 1984;34(6):798–801.CrossRefPubMed
38.
Zurück zum Zitat O’Neill GN, Aoki M, Brown RH. ABCD1 translation-initiator mutation demonstrates genotype-phenotype correlation for AMN. Neurology. 2001;57(11):1956–62.CrossRefPubMed O’Neill GN, Aoki M, Brown RH. ABCD1 translation-initiator mutation demonstrates genotype-phenotype correlation for AMN. Neurology. 2001;57(11):1956–62.CrossRefPubMed
40.
Zurück zum Zitat Pai GS, Khan M, Barbosa E, Key LL, Craver JR, Cure JK, et al. Lovastatin therapy for X‑linked adrenoleukodystrophy: clinical and biochemical observations on 12 patients. Mol Genet Metab. 2000;69(4):312–22.CrossRefPubMed Pai GS, Khan M, Barbosa E, Key LL, Craver JR, Cure JK, et al. Lovastatin therapy for X‑linked adrenoleukodystrophy: clinical and biochemical observations on 12 patients. Mol Genet Metab. 2000;69(4):312–22.CrossRefPubMed
41.
Zurück zum Zitat Pillai BK, Jasuja R, Simard JR, Hamilton JA. Fast diffusion of very long chain saturated fatty acids across a bilayer membrane and their rapid extraction by cyclodextrins: implications for adrenoleukodystrophy. J Biol Chem. 2009;284(48):33296–304. doi:10.1074/jbc.M109.043737.CrossRefPubMedPubMedCentral Pillai BK, Jasuja R, Simard JR, Hamilton JA. Fast diffusion of very long chain saturated fatty acids across a bilayer membrane and their rapid extraction by cyclodextrins: implications for adrenoleukodystrophy. J Biol Chem. 2009;284(48):33296–304. doi:10.​1074/​jbc.​M109.​043737.CrossRefPubMedPubMedCentral
42.
Zurück zum Zitat Powers JM, Schaumburg HH. Adreno-leukodystrophy (sex-linked Schilder’s disease). A pathogenetic hypothesis based on ultrastructural lesions in adrenal cortex, peripheral nerve and testis. Am J Pathol. 1974;76(3):481–91.PubMedPubMedCentral Powers JM, Schaumburg HH. Adreno-leukodystrophy (sex-linked Schilder’s disease). A pathogenetic hypothesis based on ultrastructural lesions in adrenal cortex, peripheral nerve and testis. Am J Pathol. 1974;76(3):481–91.PubMedPubMedCentral
43.
Zurück zum Zitat Powers JM, DeCiero DP, Ito M, Moser AB, Moser HW. Adrenomyeloneuropathy: a neuropathologic review featuring its noninflammatory myelopathy. J Neuropathol Exp Neurol. 2000;59(2):89–102.CrossRefPubMed Powers JM, DeCiero DP, Ito M, Moser AB, Moser HW. Adrenomyeloneuropathy: a neuropathologic review featuring its noninflammatory myelopathy. J Neuropathol Exp Neurol. 2000;59(2):89–102.CrossRefPubMed
44.
Zurück zum Zitat Raymond GV, Jones RO, Moser AB. Newborn screening for adrenoleukodystrophy: implications for therapy. Mol Diagn Ther. 2007;11(6):381–4.CrossRefPubMed Raymond GV, Jones RO, Moser AB. Newborn screening for adrenoleukodystrophy: implications for therapy. Mol Diagn Ther. 2007;11(6):381–4.CrossRefPubMed
46.
Zurück zum Zitat Schluter A, Espinosa L, Fourcade S, Galino J, Lopez E, Ilieva E, et al. Functional genomic analysis unravels a metabolic-inflammatory interplay in adrenoleukodystrophy. Hum Mol Genet. 2012;21(5):1062–77. doi:10.1093/hmg/ddr536.CrossRefPubMed Schluter A, Espinosa L, Fourcade S, Galino J, Lopez E, Ilieva E, et al. Functional genomic analysis unravels a metabolic-inflammatory interplay in adrenoleukodystrophy. Hum Mol Genet. 2012;21(5):1062–77. doi:10.​1093/​hmg/​ddr536.CrossRefPubMed
47.
Zurück zum Zitat Shulman DI, Palmert MR, Kemp SF, Lawson Wilkins Drug and Therapeutics Committee. Adrenal insufficiency: still a cause of morbidity and death in childhood. Pediatrics. 2007;119(2):e484–e494. doi:10.1542/peds.2006-1612.CrossRefPubMed Shulman DI, Palmert MR, Kemp SF, Lawson Wilkins Drug and Therapeutics Committee. Adrenal insufficiency: still a cause of morbidity and death in childhood. Pediatrics. 2007;119(2):e484–e494. doi:10.​1542/​peds.​2006-1612.CrossRefPubMed
48.
Zurück zum Zitat Smith KD, Kemp S, Braiterman LT, Lu JF, Wei HM, Geraghty M, et al. X‑linked adrenoleukodystrophy: genes, mutations, and phenotypes. Neurochem Res. 1999;24(4):521–35.CrossRefPubMed Smith KD, Kemp S, Braiterman LT, Lu JF, Wei HM, Geraghty M, et al. X‑linked adrenoleukodystrophy: genes, mutations, and phenotypes. Neurochem Res. 1999;24(4):521–35.CrossRefPubMed
49.
Zurück zum Zitat van Geel BM, Koelman JH, Barth PG, Ongerboer de Visser BW. Peripheral nerve abnormalities in adrenomyeloneuropathy: a clinical and electrodiagnostic study. Neurology. 1996;46(1):112–8.CrossRefPubMed van Geel BM, Koelman JH, Barth PG, Ongerboer de Visser BW. Peripheral nerve abnormalities in adrenomyeloneuropathy: a clinical and electrodiagnostic study. Neurology. 1996;46(1):112–8.CrossRefPubMed
50.
Zurück zum Zitat van Geel BM, Bezman L, Loes DJ, Moser HW, Raymond GV. Evolution of phenotypes in adult male patients with X‑linked adrenoleukodystrophy. Ann Neurol. 2001;49(2):186–94.CrossRefPubMed van Geel BM, Bezman L, Loes DJ, Moser HW, Raymond GV. Evolution of phenotypes in adult male patients with X‑linked adrenoleukodystrophy. Ann Neurol. 2001;49(2):186–94.CrossRefPubMed
51.
Zurück zum Zitat van Geel BM, Poll-The BT, Verrips A, Boelens J‑J, Kemp S, Engelen M. Hematopoietic cell transplantation does not prevent myelopathy in X‑linked adrenoleukodystrophy: a retrospective study. J Inherit Metab Dis. 2015;38(2):359–61. doi:10.1007/s10545-014-9797-1.CrossRefPubMed van Geel BM, Poll-The BT, Verrips A, Boelens J‑J, Kemp S, Engelen M. Hematopoietic cell transplantation does not prevent myelopathy in X‑linked adrenoleukodystrophy: a retrospective study. J Inherit Metab Dis. 2015;38(2):359–61. doi:10.​1007/​s10545-014-9797-1.CrossRefPubMed
52.
Zurück zum Zitat Vogel BH, Bradley SE, Adams DJ, D’Aco K, Erbe RW, Fong C, et al. Newborn screening for X‑linked adrenoleukodystrophy in New York State: diagnostic protocol, surveillance protocol and treatment guidelines. Mol Genet Metab. 2015;114(4):599–603. doi:10.1016/j.ymgme.2015.02.002.CrossRefPubMed Vogel BH, Bradley SE, Adams DJ, D’Aco K, Erbe RW, Fong C, et al. Newborn screening for X‑linked adrenoleukodystrophy in New York State: diagnostic protocol, surveillance protocol and treatment guidelines. Mol Genet Metab. 2015;114(4):599–603. doi:10.​1016/​j.​ymgme.​2015.​02.​002.CrossRefPubMed
53.
Zurück zum Zitat Whitcomb RW, Linehan WM, Knazek RA. Effects of long-chain, saturated fatty acids on membrane microviscosity and adrenocorticotropin responsiveness of human adrenocortical cells in vitro. J Clin Invest. 1988;81(1):185–8. doi:10.1172/JCI113292.CrossRefPubMedPubMedCentral Whitcomb RW, Linehan WM, Knazek RA. Effects of long-chain, saturated fatty acids on membrane microviscosity and adrenocorticotropin responsiveness of human adrenocortical cells in vitro. J Clin Invest. 1988;81(1):185–8. doi:10.​1172/​JCI113292.CrossRefPubMedPubMedCentral
Metadaten
Titel
Therapeutic strategies in adrenoleukodystrophy
verfasst von
Bela R. Turk
Ann B. Moser
Ali Fatemi
Publikationsdatum
10.05.2017
Verlag
Springer Vienna
Erschienen in
Wiener Medizinische Wochenschrift / Ausgabe 9-10/2017
Print ISSN: 0043-5341
Elektronische ISSN: 1563-258X
DOI
https://doi.org/10.1007/s10354-016-0534-2

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