Therapeutic strategies in adrenoleukodystrophy

Bela R. Turk, Ann B. Moser, Ali Fatemi

Research output: Research - peer-reviewArticle

Abstract

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.

Translated title of the contributionTherapeutic strategies in adrenoleukodystrophy
LanguageGerman
Pages1-8
Number of pages8
JournalWiener Medizinische Wochenschrift
DOIs
StateAccepted/In press - May 10 2017

Fingerprint

Adrenoleukodystrophy
Therapeutics
Mutation
Genes
Spinal Cord Diseases
Poisons
Hematopoietic Stem Cell Transplantation
Genetic Association Studies
Demyelinating Diseases
Peripheral Nervous System Diseases
Carrier Proteins
Oxidative Stress
Cell Death
Fatty Acids
Newborn Infant
Pathology

Keywords

  • Demyelinating Diseases
  • Hematopoietic Stem Cell Transplantation
  • Leukoencephalopathies
  • Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Therapeutische Strategien bei Adrenoleukodystrophie. / Turk, Bela R.; Moser, Ann B.; Fatemi, Ali.

In: Wiener Medizinische Wochenschrift, 10.05.2017, p. 1-8.

Research output: Research - peer-reviewArticle

@article{3a42df37375b48fd9a012fe935e57788,
title = "Therapeutische Strategien bei Adrenoleukodystrophie",
abstract = "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.",
keywords = "Demyelinating Diseases, Hematopoietic Stem Cell Transplantation, Leukoencephalopathies, Therapeutics",
author = "Turk, {Bela R.} and Moser, {Ann B.} and Ali Fatemi",
year = "2017",
month = "5",
doi = "10.1007/s10354-016-0534-2",
pages = "1--8",
journal = "Wiener Medizinische Wochenschrift",
issn = "0043-5341",
publisher = "Springer Wien",

}

TY - JOUR

T1 - Therapeutische Strategien bei Adrenoleukodystrophie

AU - Turk,Bela R.

AU - Moser,Ann B.

AU - Fatemi,Ali

PY - 2017/5/10

Y1 - 2017/5/10

N2 - 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.

AB - 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.

KW - Demyelinating Diseases

KW - Hematopoietic Stem Cell Transplantation

KW - Leukoencephalopathies

KW - Therapeutics

UR - http://www.scopus.com/inward/record.url?scp=85019082440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019082440&partnerID=8YFLogxK

U2 - 10.1007/s10354-016-0534-2

DO - 10.1007/s10354-016-0534-2

M3 - Article

SP - 1

EP - 8

JO - Wiener Medizinische Wochenschrift

T2 - Wiener Medizinische Wochenschrift

JF - Wiener Medizinische Wochenschrift

SN - 0043-5341

ER -