Chemical 'Signature' May Be Used to Track ALS

by Amy Madsen on Wed, 2012-08-29 05:00

A biomarker in the blood may indicate the earliest stages of ALS and provide a way to monitor disease progression using a blood test

Article Highlights:
  • Monocytes (white blood cells) display a chemical signature associated with inflammation prior to disease onset in mice with a disease resembling ALS caused by mutations in the SOD1 gene.
  • A similar signature is found in the monocytes of people who have familial ALS caused by mutations in SOD1, and researchers suggest that common pathways may be affected in other forms of ALS as well. 
  • Targeting the monocytes in mice leads to less motor neuron loss and a slower rate of disease progression.

A "pro-inflammatory" chemical signature displayed by monocytes (a type of white blood cell) appears to signal the presence of amyotrophic lateral sclerosis (ALS) even before symptoms begin, a team of scientists has reported. If verified, the blood biomarker may make it possible for physicians to monitor disease progression using a simple blood test.

In the SOD1 research mouse model of ALS, the researchers found that monocytes developed a "pronounced" pro-inflammatory profile one month before disease onset. After developing the distinct signature, the cells moved from the spleen to the spinal cord, where they increased inflammation and multiplied as the disease progressed.

When scientists used immune system proteins called antibodies to target the monocytes in the mice, they found they slowed motor neuron loss — the hallmark of ALS — and decreased the rate of disease progression.

A similar signature found in the monocytes of people with familial SOD1-related ALS "provides a direct link between the animal model and the human disease,” say the investigators. In addition, they noted, the immune abnormalities may "represent common pathways that are affected in different forms of ALS."

The findings support the idea that the immune system is activated before disease onset and that inflammation plays a key role in ALS.

The study team, led by Howard L. Weiner at Brigham and Women's Hospital and Harvard Medical School in Boston, published its findings online Aug. 6, 2012, in the Journal of Clinical investigation. Read the full report, free of charge: Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS.

The findings suggest that modulation of monocytes may be a potential therapeutic strategy in ALS. This strategy is currently under development using several different compounds:

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