Holes in the Walls

Proteins that keep large molecules from moving freely across blood-vessel walls in the spinal cord appear to be deficient in people with ALS (amyotrophic lateral sclerosis), MDA-supported researchers say. They don't yet know, however, whether a lower-than-normal level of some of these so-called "tight junction" proteins, is helpful or harmful in the disease process.

Neurologist and MDA grantee Stanley Appel, who directs the MDA/ALS Center at Methodist Neurological Institute in Houston, and colleagues, published their findings in the May 5, 2009, issue of the journal Neurology.

The researchers measured levels of messenger RNA, the final genetic instructions from which a cell makes a protein, in spinal cord samples from 30 people with sporadic (nonfamilial) ALS, four with familial ALS and a control group of 16 people with no neurodegenerative disease.

They found the messenger RNA for the tight junction protein called zona occludens 1 (ZO1) was lower in lumbar spinal cord tissue in people with sporadic ALS compared to tissue from the control group. There was no difference in the RNA for ZO1 in the four familial ALS samples compared to the control group.

Messenger RNA levels for another tight junction protein, occludin, were lower in lumbar spinal cord samples from people with familial ALS than they were in samples from the control group, but there was no difference between the sporadic ALS samples and control group samples.

RNA levels for a third tight junction protein were the same in the ALS samples as a whole and the control samples.

The researchers note that previous studies have suggested that the vascular barrier between the bloodstream and the spinal cord, known as the "blood-spinal cord barrier," is leakier than normal in ALS, and they say this study adds further support to that evidence.

They say the leakiness could lead to the entry of toxic molecules into the spinal cord and contribute to the nerve-cell damage that characterizes ALS.

Conversely, they note, the enhanced permeability could allow the entry of immune-system cells that have been associated with protection of nerve cells in this disease.

If the first scenario proves to be the case, they say, then preserving the integrity of the blood-spinal cord barrier may represent a target for therapeutic development.

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