Researchers Seek Signposts to Diagnose, Monitor and Treat ALS

by Margaret Wahl on Sun, 2009-03-01 09:16
doctor and patient
Investigators are looking for an ALS-specific “profile” in blood and spinal-fluid samples.

When investigators coordinated by James Connor at Pennsylvania State University College of Medicine in Hershey compared spinal fluid samples from 41 people with ALS to samples from 33 people with other neurologic diseases to see whether they could develop an ALS-specific “profile,” they found several proteins that were more abundant in the ALS than the non-ALS group.

The investigators, who published their report in the Jan. 6, 2009, issue of Neurology, also found some evidence that ALS may be associated with variations in a gene called HFE, which affects inflammation, immunity and iron regulation.

Such profiles, made up of various biological indicators, or “biomarkers,” may not sound like exciting research, but they’re crucial for accurate diagnosis and tracking responses to treatment. They may also yield insights into disease causation and suggest new possibilities for therapy.

The spinal fluid, also known as cerebrospinal fluid (CSF), which bathes the brain and spinal cord, is believed to be a good source of ALS biomarkers because of its close proximity to the sites of injury in this disease.

The five protein biomarkers that were the most significantly different in the ALS group’s CSF compared to the non-ALS neurologic disease group were interleukins 2, 6, 10 and 15, and granulocyte-monocyte colony stimulating factor. All were found at higher levels in the ALS group, and all either augment or counter inflammation or other activities of the immune system.

The authors say their findings don’t clarify whether inflammatory processes precede disease onset or result from it, but they do reveal inflammatory activity early in the disease process. Their results, they say, are “consistent with the overall concept that microglia [immune cells of the nervous system] recruitment and activation are key components of ALS pathogenesis.”

They note that their data expand those of previous studies and show promise that a biomarker profile of ALS can be developed. Future studies, they suggest, should involve larger numbers of ALS patients with HFE gene variations and patients with ALSlike diseases that aren’t ALS; and they suggest analyzing CSF samples from various time points in the disease to see what changes may correlate with progression.

The MDA-supported ALS Therapy Development Institute (ALS TDI) in Cambridge, Mass., has analyzed some 250 human blood samples in search of ALS-specific biomarkers and hasidentified some preliminary candidates. To ask about participation, contact Beth Levine of ALS TDI at (617) 441-7200 or

A multicenter study to identify differences in blood and CSF biomarkers between people with ALS and those with other neurological diseases is also seeking participants. Samples will be part of a large repository available to researchers studying ALS, and the samples also will help better understand the cause of these different disorders.

Sites are in California, Florida, Georgia, Illinois, Maryland, Massachusetts, Missouri, New Jersey, New York, New Hampshire, North Carolina, Oregon, Pennsylvania and Utah. Merit Cudkowicz, who heads up the MDA ALS Center at Massachusetts General Hospital in Boston, and Swati Aggarwal, also at Mass General, are the principal investigators.

The study involves blood draws, a lumbar puncture (needle inserted into fluid around spinal cord) to obtain CSF, and collection of disease-related information.

If interested, call the toll-free number at (877) 458-0631.

Margaret Wahl
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