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: Genes modify the risk of liver disease among alcoholics

Related Stories

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

Competing mice reveal genetic defects

September 30, 2015

In recent years, University of Utah biologists showed that when wild-type mice compete in seminatural "mouse barns" for food, territory and mates, they can suffer health problems not revealed by conventional toxicity tests ...

Maintaining healthy DNA delays menopause

September 28, 2015

An international study of nearly 70,000 women has identified more than forty regions of the human genome that are involved in governing at what age a woman goes through the menopause. The study, led by scientists at the Universities ...


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.