Using gene therapy to tackle complex brain disease

June 13, 2013
Using gene therapy to tackle complex brain disease
Credit: Shutterstock

Substantial progress has been made in the development of treatments for a particular brain disease, thanks in part to an EU-funded project. The X-ALD project focused on achieving a better understanding of the pathogenic mechanisms leading to 'X-linked adrenoleukodystrophy', a disorder which results in the accumulation of long chain fatty acids in tissues throughout the body but especially in the central nervous system.

Most importantly, this research could open the door to the further development of novel therapeutic approaches. Researchers found for example that X-ALD could be treated with a combination of gene therapy and blood .

'The main results of this project were the improved understanding of the molecular mechanism of X-ALD,' explains project coordinator Johannes Berger. 'Although we still don't fully understand the detailed mechanism, we have nonetheless moved substantially forward, something which is visible by the many papers published in journals such as Science and Nature Medicine. In addition, a novel strategy for the treatment of patients with an inflammatory form of X-ALD and have no has been developed.'

X-ALD is one of the most common monogenetic disorders affecting the (CNS). Ultimately the - the protective layer that coats the nerves - is destroyed, causing . Patients who have no myelin succumb to mental and physical problems triggered by nerves that lose their function.

All forms of X-ALD are characterised by neurological abnormalities, which in the most severe cases can be fatal. While X-ALD is characterised biochemically by the accumulation of fatty acids, the role of this acid accumulation in the pathophysiology of the disease has remained a mystery. However, the X-ALD team has made substantial progress in the identification of candidates for modifier genes that could account for the phenotypic variability in the expansion and characterisation of X-ALD.

The gene affected in X-ALD codes for a protein that is probably involved in the transport of very into a specific intracellular organelle, called the peroxisome. To this end, the project team developed a new system in which the properties of ALD protein can be studied under in vivo conditions using baker's yeast, as well as an in vitro system.

'X-ALD is a rare disease, and very little was known about the underlying it,' explains Professor Berger. 'By bringing together experts in the field, we managed to achieve a major breakthrough in our understanding of the disease, and opened up novel therapeutic strategies that are now in clinical use.'

With respect to gene therapy, this project has moved even beyond the original scope to the first clinical application of gene therapy in X-ALD. A major impact of the work carried out in this project is expected with regard to future therapeutic treatment of X-ALD patients within the next 10 years.

Professor Berger believes that intense discussions and regular meetings enabled the project team to achieve focus. 'We were able to drive each other forward, and this was the main reason for the success of the project,' he says. 'The group has continued to work together, and has focused on other forms of the disease where there are still no treatments available.'

More information: X-ALD www.x-ald.nl

Related Stories

Adrenoleukodystrophy unravelled

July 30, 2012

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 ...

Binge drinking can dramatically amplify damage to the liver

January 22, 2013

Alcoholic liver disease (ALD) is characterized by a fatty liver, hepatitis, fibrosis, and cirrhosis. Binge drinking is on the rise worldwide, and is particularly common in the U.S. A review of studies addressing the effects ...

Recommended for you

A cheaper, high-performance prosthetic knee

July 30, 2015

In the last two decades, prosthetic limb technology has grown by leaps and bounds. Today, the most advanced prostheses incorporate microprocessors that work with onboard gyroscopes, accelerometers, and hydraulics to enable ...

Crystal clear images uncover secrets of hormone receptors

July 31, 2015

Many hormones and neurotransmitters work by binding to receptors on a cell's exterior surface. This activates receptors causing them to twist, turn and spark chemical reactions inside cells. NIH scientists used atomic level ...

Flow means 'go' for proper lymph system development

July 27, 2015

The lymphatic system provides a slow flow of fluid from our organs and tissues into the bloodstream. It returns fluid and proteins that leak from blood vessels, provides passage for immune and inflammatory cells from the ...

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.