Amyotrophic Lateral Sclerosis (ALS) Treatment : Part 2

by Food and Drug Administration (FDA)

(Page 2 of 2)

Because too much glutamate can be toxic, the brain usually regulates the substance, keeping levels to those needed for body functioning. Abnormally high levels of glutamate have been found in the cerebrospinal fluid (the clear watery fluid that surrounds the brain and the spinal cord) of some patients with ALS.

In experiments, scientists have found that a protein responsible for removing excess glutamate from the brain appears not to work properly in people with ALS. They theorize that toxicity resulting from excessive glutamate might be killing motor neurons. The death of these cells leads to progressive muscle wasting in patients with ALS. One of the characteristics of Rilutek is that it inhibits the release of glutamate in the brain.

Rilutek is taken by mouth. Everyone who takes the drug must be monitored regularly for signs of Rilutek's most important side effect, a rise in the level of liver enzymes, which indicates abnormal liver function.

The drug's labeling states that treatment should be discontinued if liver enzymes increase to 10 times their normal level.

About five out of every 100 people who get ALS have an inherited, or familial, form of the disease; that is, one or more of their immediate family members — parents, brothers, sisters, or grandparents — also have the disease. Children of people with familial ALS have a fifty-fifty chance of developing the disease themselves.

In 1993, scientists identified a gene that, when defective, is associated with some cases of familial ALS. This gene carries the operating instructions for a protein whose function is to neutralize cell-damaging substances called free radicals. Some scientists think that when the gene is defective, an excessive buildup of free radicals may kill motor neurons.

However, this genetic mutation is found in only about one-fifth of people with familial ALS, according to Rothstein, and it has not been detected in anyone with the sporadic (noninherited) form of the disease, which is far more common.

Searching for Treatments

Even if the cause of the disease is eventually found, the development of effective treatments presents enormous challenges, said Rothstein. "The drugs have to be potent and they have to get into the nervous system, which has a very tight barrier — the blood-brain barrier — that prevents entry by many drugs."

Some doctors think that neurotrophic growth factors, substances produced by the body that stimulate nerve cells to grow and multiply, may be useful for treating ALS. These substances can now be produced in the laboratory using the techniques of biotechnology. Myotrophin is one such factor.

"No one thinks that neurotrophic factors, or the lack of them, cause ALS," said Rothstein. "But in animal experiments they seem to work quite well in preventing injury to motor neurons."

FDA's Walton said the agency is working with investigators and the drugs' manufacturers to try to design trials "that will tell us as quickly and efficiently as possible whether or not these products can be effective in the treatment of ALS."

Until more effective drugs are developed and approved to treat ALS, measures to improve patients' mobility and quality of life remain the mainstay, said Rothstein. "Nutrition is very important. A recent study in Italy showed increased survival in ALS patients who received good nutrition using a feeding tube.

"There's also a mask that patients can use to assist their breathing, and physical therapy can help to make them more comfortable. A speech pathologist can help them to learn different swallowing techniques as their swallowing muscles become weaker. Support groups for patients and their families are also very important."

On Sept. 6, 1995 — the day Cal Ripken Jr. broke Lou Gehrig's record for consecutive games played — the Baltimore Orioles and the Johns Hopkins Medical Institutions announced the launch of the Cal Ripken/Lou Gehrig Fund for Neuromuscular Research.

Ticket sales to the record-breaking game and an Orioles contribution raised $2 million for the fund. Kuncl said the money will support research at Johns Hopkins on neuromuscular diseases, with an emphasis on ALS.

Johns Hopkins' Rothstein said that though the drugs available do not thus far seem to give dramatic improvement, he is not discouraged.

"This is against the background of decades when no drug ever did anything for the disease. Initial therapies for many diseases, like leukemia and other cancers, had the same kind of effect ... a modest increase in survival. But they were followed by better therapies that, over time, increased patients' survival.

"It's a daunting task, but I envision that some day it will be possible to develop drugs that will not only stop motor neurons from dying but replace them and reverse the course of ALS."

Exceptional Survivor

The brilliant British theoretical physicist Stephen W. Hawking, who is probably best known to the general public as the author of A Brief History of Time, is one of a very few people who have survived for many years with amyotrophic lateral sclerosis (ALS).

Hawking, now 54, was diagnosed with ALS in 1963 when he was a 21-year-old graduate student at Cambridge University in England.

Hawking's life demonstrates that ALS impairs neither intellect nor sexual function. His work on the origin and nature of the universe has been, in the words of biographers Michael White and John Gribbin, "ground-breaking and revolutionary." Hawking also married and fathered three children after his diagnosis.

In 1985, after suffering a windpipe blockage, Hawking had a breathing device surgically implanted in his throat. The surgery resulted in the loss of his voice. He now "speaks" by using a voice synthesizer connected to a computer that he operates by squeezing a switch in his hand.

In Stephen Hawking: A Life in Science, White and Gribbin write that Hawking has a very strong personality and has "never [given] in to the symptoms of ALS more than he is physically compelled to."

About the Author

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