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Immune system and inflammation linked to Lou Gehrig's disease

Robin Wulffson MD's picture
ALS, amyotrophic lateral sclerosis, Alzheimer's disease, stroke, brain injury

A new study by UCLA researchers has found a link between the immune system and amyotrophic lateral sclerosis (ALS). The condition, also known as Lou Gehrig’s disease, is a progressive and debilitating disorder of the nerve cells in the brain and spinal cord that control voluntary muscle movement. The research could lead to new therapies to treat ALS as well as other neurodegenerative disorders such as Alzheimer’s disease. The findings were published in the May 30 edition of the peer-reviewed American Journal of Neurodegeneration.

The authors note that inflammation is increasingly being recognized as a pathophysiological mechanism in neurodegenerative diseases such as ALS. For the study, the team isolated macrophages (cells responsible for gobbling up waste products in the brain and body) from blood samples taken from both ALS patients and healthy controls. In addition, they evaluated spinal cord cells from deceased donors. The researchers compared inflammatory responses in ALS patients and compared them to the healthy controls. They found that inflammation initiated by the immune system in ALS can trigger macrophages to also ingest healthy neurons. During the inflammation process, motor neurons, whether healthy or not, are marked for clean-up by the macrophages.

Senior author Dr. Milan Fiala, a researcher in the department of surgery at the David Geffen School of Medicine at UCLA, and colleagues found that a lipid mediator called resolvin D1, which is made in the body from the omega-3 fatty acid DHA, was able to “turn off” the inflammatory response that made the macrophages so dangerous to the neurons. Resolvin D1 blocked the inflammatory proteins being produced by the macrophages, curbing the inflammation process that marked the neurons for clean-up. It inhibited key inflammatory proteins such as IL-6 with a potency 1,100 times greater than the parent molecule, DHA. DHA has been shown in studies to be neuroprotective in a number of conditions, including stroke and Alzheimer’s disease.

The researcher team notes that the study findings on resolvin D1 may offer a new approach to reducing the inflammation in ALS. The note that currently, there is no effective way of administering resolvins to patients; therefore, clinical research with resolvin D1 is still several years away. However, the parent molecule, DHA, is available. To date, DHA has not been tested in clinical trials for ALS. Studies with DHA are in progress for Alzheimer’s disease, stroke, and brain injury and have been mostly positive.

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The alternative name for ALS, Lou Gehrig’s disease, was given in recognition of the New York Yankees baseball player who was diagnosed with the disease in 1939. ALS affects approximately 1 out of every 100,000 people. In about 10% of cases, ALS is caused by a genetic defect. In other cases, the cause is unknown. In ALS, nerve cells (neurons) waste away or die, and can no longer send messages to muscles. As a result, muscles gradually weaken and a person becomes unable to move his or her arms or legs.

This eventually leads to muscle weakening, twitching, and an inability to move the arms, legs, and body. Naturally, people with this condition have difficulty to breath on their own when the muscles in the chest area stop working.

Except for having a family member who has a hereditary form of the disease, there are no known risk factors. Symptoms usually do not develop until after age 50. Individuals with ALS have a loss of muscle strength and coordination that eventually gets worse. As the disease progresses, it becomes difficult to do routine tasks such as going up steps, getting out of a chair, or swallowing. Breathing or swallowing muscles may be the first muscles affected. As the disease gets worse, more muscle groups develop problems. ALS does not affect the senses (sight, smell, taste, hearing, touch), bladder or bowel function, or a person’s ability to think or reason.

There is no known cure for ALS. The first drug treatment for the disease is a medicine called riluzole. Riluzole may prolong life; however, it does not reverse or stop the disease from getting worse. The current goal of treatment is to control symptoms. Baclofen or diazepam may be used to control spasticity that interferes with activities of daily living. Trihexyphenidyl or amitriptyline may be prescribed for people with problems swallowing their own saliva. Physical therapy, rehabilitation, use of braces or a wheelchair, or other orthopedic measures may be needed to maximize muscle function and general health.

American Journal of Neurodegeneration
UCLA Health System