With funding from the A-T Children’s Project, Stefan Zielen and Ralf Schubert from the Goethe University in Frankfurt, Germany will examine spinal fluid from children and adolescents with A-T in an attempt to identify measurable indicators of oxidative stress, inflammation, or tissue breakdown that correlate with disease progression and severity.

Spinal fluid, the clear fluid flowing around the brain and spinal cord, often contains markers of central nervous system disease. These markers can be valuable indicators of disease progression and severity. And, if a reliable marker were discovered for A-T, it could be used to evaluate responses to therapeutic interventions.

Many studies have shown that cells obtained from A-T patients and grown in a laboratory dish, as well as A-T mice, possess signs of oxidative stress and elevated reactive oxygen species, but only a couple of studies have hinted that oxidative stress and inflammation actually occur in the bodies of people with A-T.

Several years ago, a separate laboratory funded by the A-T Children’s Project examined the overall expression of proteins in spinal fluid from adults with advanced A-T. The published results from that study showed that the expression of at least 13 proteins, involved either in neurodegeneration or cancer, was altered in people with A-T compared to healthy individuals. That study, however, did not look at younger A-T patients to see how protein levels changed.

Now, Drs. Zielen and Schubert will look specifically for markers of oxidative stress, inflammation and degeneration in spinal fluid from young patients at several time points earlier in the disease process. If they succeed in identifying disease biomarkers for A-T, clinicians and scientists will have a powerful tool to track disease severity and changes in severity during clinical trials. The biological function of the discovered markers may also provide valuable clues about the underlying cause of brain cell death in A-T.

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