White Matter Matters... p.1

Adrenoleukodystrophy (ALD) is a neurodegenerative disorder, and although it is not an infectious disease, which is the focus of this blog, there has been some groundbreaking research recently published regarding this chronic illness that I am excited to write about.

Background information: ALD is an X-linked recessive disorder, indicating it is most commonly found among males and is inherited from the mother. It is characterized by an accumulation of very long-chain fatty acids in the brain, spinal cord, and plasma, which in turn destroy myelin sheath in the nervous tissue.

Very long-chain fatty acids are typically produced within the body and are transported into the peroxisome where they are broken down through β-oxidation. Myelin sheath is the white matter, or layer of lipid fats and proteins, “insulating” the axon of a nerve cell.

Figure 1: Very Long-Chain Fatty Acid Photo Credit: < http://www.x-ald.nl/biochemistry.htm>

The demyelination exhibited in ALD leads to vision loss, impaired coordination, difficulty swallowing, dementia, and paralysis. This illness is most commonly diagnosed at a young age and typically results in death within 2-4 years after diagnosis. At present, there is no general curative therapy for ALD. Traditionally, adrenal steroid replacement therapy and “Lorenzo’s Oil” has been used as treatment; however, both have little to no effect on neurological symptoms. A recent therapeutic method is hematopoietic cell transplantation (HCT), or in other words, bone marrow transplantation. HCT stops cerebral demyelination, thereby arresting the disease progression. Despite the apparent benefits to this treatment, this procedure puts the patient at a very high risk.

Figure 2: Brain MRI scans of 10-year-old, male, ALD patient Photo Credit: Tolar, et al. 2007

Figures 2, images A—D depict the MRI scans of an ALD patient, prior to HCT. Extensive inflammation and an abnormally high presence of white matter are observed in the various regions of the brain. Figures 2 E—H depict the MRI scans of the patient, 3 months after treatment. A significant decrease in white matter is observed; however, atrophy and deterioration of the actual brain tissue is also seen.

References: X-linked Adrenoleukodystrophy Database. Kennedy Krieger Institute, Human Genome variation Society, & Academic Medical Center University of Amsterdam. http://www.x-ald.nl/ (last updated 19 Nov 2009, accessed Dec 2009)

Tolar J., P.J. Orchard, K.J. Bjoraker, R.S. Ziegler, E.G. Shapiro & L. Charnas. N-acetyl-L-cysteine improves outcome of advanced cerebral adrenoleukodystrophy. Bone Marrow Transplantation 39:211--215 (2007).