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Focusing on glial cells to overcome an intractable disease, ALS

Amyotrophic lateral sclerosis (ALS) is a devastating disease, gradually causing paralysis of the muscles in the hand and leg. The discovery by Koji Yamanaka and colleagues at the Brain Science Institute that the glial cells cause damage to the nerve cells shows great promise in the development of new treatments to prevent the progression of ALS.

Amyotrophic lateral sclerosis (ALS) is a devastating disease. Once ALS develops, the motor neurons that control the movement of muscles gradually start to die off, causing paralysis of the muscles in the hand and leg.

The patient suffers from difficulty in using arms and legs, and in eating food and speaking. In about two to five years after the development of ALS, the muscles that control breathing are paralyzed, necessitating the support of a respirator. However, because the senses, memory, and cognitive functions remain normal, the patient is conscious of the progression of the disease.

Unfortunately, no effective treatment has been found. So far, research into understanding ALS has focused mainly on motor neurons. However, Koji Yamanaka, Unit Leader, and colleagues at the Brain Science Institute has focused on cells neighboring the motor neurons, and have met with success in their discovery that the glial cells cause damage to the nerve cells, thus accelerating the progression of the disease. This discovery shows great promise in the development of new treatments to prevent the progression of ALS.

ALS, an incurable disease that exclusively destroys motor neurons

In the spring of 1939, Lou Gehrig, a Major League Baseball player for the New York Yankees in the US, was mired in a prolonged batting slump. His fans and team-mates were very surprised because he was a real slugger, who enjoyed many seasons with high batting averages; his batting record included 23 grand slam home runs, a Major League record, and a consecutive game-playing streak of 2130. He was called "Iron Horse," but it was ALS that prevented him from continuing his playing streak. Lou Gehrig retired in June that year. Two years later he died young, at the age of 37 years.

In the US, ALS is known as 'Lou Gehrig's disease' and is one of the neurodegenerative diseases caused by the gradual death of nerve cells. In Alzheimer's disease, which is a well-known neurodegenerative disease, the patient develops dementia as a result of the gradual death of memory-related nerve cells. In ALS, in contrast, the patient becomes paralyzed because of the gradual death of the motor neurons in the brain and the spinal cord that control the muscles throughout the body.

There are about 6,000 patients with ALS and it is estimated that about 2,000 people may develop ALS every year in Japan. Patients with ALS develop the disease mostly at about 60 years of age, but young people can be affected, like Gehrig.

About 10% of patients with ALS develop the disease because they have inherited the causative genes, but no abnormal genes were found in the remaining 90%. "In other words, anybody can develop ALS," says Yamanaka, who has worked as a neurologist and has treated patients with ALS.

Neurologists are the medical doctors who have been trained in the diagnosis of diseases of brain, spinal cord, and muscle, and their treatment with drugs. In fact, however, there are many other diseases that cannot be treated with drugs because the causes are unknown. "I faced a big dilemma in clinical practice, seriously thinking, 'What can I provide for patients with ALS?' So, I thought I would like to elucidate the cause of the neurodegenerative disease to develop new cures."

Yamanaka trained and worked as a neurologist for four years. Then he devoted himself to basic research and started the study on ALS in 2001. Why did he select ALS as his subject of research? "I chose ALS because it is an incurable disease. ALS progresses quickly, and the symptoms of the patient worsen day by day. From the time the patient makes a clinical visit, he or she will be unable to walk within the first year, will be bed-ridden within the following year, and won’t be alive within three years from the first visit. I was greatly motivated by shocking experiences when I was responsible as a neurologist for treating patients with ALS."

Saeko Okada | ResearchSEA
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