New Studies Support Roles of Inflammation, Oxidative Stress in ALS

by Margaret Wahl on Mon, 2004-03-01 07:00

Three new studies confirm the roles of two long-suspected factors in the development and perpetuation of ALS.

Inflammation is a set of biochemical changes brought about by the immune system, while oxidative stress occurs when an excess of electrically charged, oxygen-containing molecules damage DNA and other cellular substances.

Inflammation

David Jayne
Robert Brown

Robert Brown, director of the MDA/ALS Center at Massachusetts General Hospital in Boston, was among the authors of a study of inflammation published in the Jan. 15 issue of Physiological Genomics.

The researchers looked at postmortem samples of spinal cord tissue. They found a definite "pro-inflammatory state" in the ALS tissue compared with samples from people who didn’t have ALS.

They also found that genes involved in the inflammatory process in ALS were selectively activated. (This finding doesn’t imply anything is wrong with the structure of the genes; it means they’re "turned on" because of the inflammatory process instead of being in their usual "turned off" condition.)

Stanley Appel, director of the Ronny & Linda Finger MDA/ALS Center at Baylor College of Medicine in Houston and an MDA research grantee, was part of the team that conducted another ALS tissue study, published in the February issue of Annals of Neurology.

David Jayne
Stanley Appel

In this study, the researchers also compared postmortem spinal cord tissue samples. They looked for evidence of dendritic cells, key players in an inflammatory response in the nervous system, and for traces of the chemical messenger MCP-1, which can recruit these cells from the blood into the nervous system.

They found that both dendritic cell surface markers and MCP-1 were elevated in the tissue from ALS patients.

Two drugs — minocycline and celecoxib (Celebrex) — that combat inflammatory responses are now being investigated in ALS clinical trials.

Oxidative stress

In the third study, published in the Jan. 27 issue of Neurology, Appel and MDA research grantee Jenny Henkel were authors. The researchers found that an enzyme that repairs damaged DNA was elevated in several areas of ALS brain tissue, not just in the areas that control muscle movement.

The enzyme, known as PARP, is apparently brought into play when oxidative stress has damaged DNA.

The investigators concluded that widespread oxidative damage to DNA occurs in the brains of people with ALS and that some parts of the brain are able to resist or repair it. Other areas, particularly the motor neurons (which control muscle movement), apparently can’t keep up with the devastation.

The researchers suggest that the lack of damage in other brain areas could be due to a superior ability to handle calcium on the part of these cells.

Margaret Wahl
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