Adrenoleukodystrophy unravelled

July 30, 2012
Adrenoleukodystrophy unravelled
Credit: Thinkstock

The European X-ALD project undertook an initiative to understand the mechanisms responsible for the pathogenesis of adrenoleukodystrophy (ALD). The gene therapy approach for treating ALD developed during the study brings hope to many young boys that have inherited the disease.

ALD is a progressive metabolic that occurs approximately in 1 in 17,000 newborns. It is caused by mutations in the ABCD1 gene located on the and affects the of the . Biochemically, X-linked ALD (X-ALD) is characterised by transport deficiency of very long-chain fatty acids (VLCFAs).

Accumulating evidence suggests that the ABCD1 gene codes for a protein that is probably implicated in the transport of VLCFAs into a specific intracellular organelle, called the . To this end, a model based on the yeast S. cerevisae has been developed to study the function of ALD protein.

Using this model, the EU-funded ‘X-linked Adrenoleukodystrophy (X-ALD): pathogenesis, animal models and therapy’ (X-ALD) project aimed to prove the role of ALD protein in VLCFA transport. Expression of ALD protein in genetically engineered yeast cells was capable of restoring the defective transport of VLCFAs. In vitro experiments using mammalian peroxisomes verified the yeast findings, conclusively demonstrating for the first time the function of the ALD protein.

Furthermore, project scientists developed new X-ALD mouse models which helped them identify candidates for modifier genes that could account for the phenotypic variability seen in ALD patients. The substantial progress made towards the understanding of the pathogenic mechanisms underlying the disease has aided the development of novel therapeutic approaches and the first clinical application of gene therapy in X-ALD.

The X-ALD work carried out in this project is expected to have significant implications with regards to future therapeutic treatment of X-ALD patients.

Explore further: New clinical practice guidelines on alcoholic liver disease published

Related Stories

New clinical practice guidelines on alcoholic liver disease published

April 19, 2012
EASL today announced the publication of a new clinical practice guideline (CPG) in the area of Alcoholic Liver Disease (ALD), bringing the number of CPGs published to date to eight.

Genes modify the risk of liver disease among alcoholics

December 6, 2011
It has been widely observed that only a small percentage of alcoholics develop cirrhosis of the liver, the most advanced form of alcoholic liver disease (ALD); the reason why all alcoholics do not develop such disease is ...

Recommended for you

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

Newly identified genetic marker may help detect high-risk flu patients

July 17, 2017
Researchers have discovered an inherited genetic variation that may help identify patients at elevated risk for severe, potentially fatal influenza infections. The scientists have also linked the gene variant to a mechanism ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.