Gehrig’s Disease Clinical Trials Near : Medicine: Discovery of the defective gene that causes amyotrophic lateral sclerosis prompts a rush to begin potential treatments. Nearly all U.S. patients will be eligible.
Only three weeks after discovery of the defective gene that causes amyotrophic lateral sclerosis, better known as Lou Gehrig’s disease, researchers are racing to begin clinical trials of the first potential treatments for the disorder, which previously had been untreatable.
Virtually every one of the 30,000 ALS patients in the United States will be able to enter a trial, doctors said this week. Scientists discovered that the disorder may be caused by the loss of the body’s antioxidant, a substance that prevents damage to cells. This has led researchers to conclude that other antioxidants such as Vitamins C and E and beta-carotene, as well as some prescription drugs, may halt progression of the disorder.
“We know the drugs are safe in humans, and this is a disease that kills people in two to three years,” said Dr. Arnold Gale, a neurologist with the Muscular Dystrophy Assn. “If we did not undertake these trials immediately, we would be completely lacking in compassion,” Gale said during a planning visit to Los Angeles this week.
The trials could begin in two months. They will be held nationwide at the five MDA-supported ALS centers, including one at USC, as well as the organization’s 240 clinics, such as one at UCLA. Patients hoping to participate in the trials should call (800) 572-1717.
But the task of proving which treatment, if any, is effective will be difficult because a substantial number of ALS patients undoubtedly began medicating themselves with the vitamins as soon as they learned the nature of the defective gene, said Dr. W. King Engel, a USC neurologist. “It isn’t going to be easy,” he said.
The clinical trials will be unlike normal drug trials in some very important aspects. In most clinical trials of new drugs or therapies, only a small fraction of the patients with a disease get into the initial trials. Researchers want to include as many ALS patients as possible, however, both because they want to maximize the number of regimens they can study and because the patients will die otherwise.
“This isn’t acne we’re dealing with,” Gale said.
Second, instead of enrolling hundreds or thousands of patients in one large trial testing a single approach, as is normally done, physicians now envisage creating many smaller groups that will each receive a different treatment regimen.
“We’re taking a SWAT-team approach by planning small studies that can quickly get us answers,” said Dr. Robert Brown Jr., a neurologist at Massachusetts General Hospital who led the team that discovered the defective gene. “We hope to get results in weeks, not months,” added Dr. Norine Stirpe, director of research development for the Muscular Dystrophy Assn., which is both funding and coordinating the trials.
And finally, everyone in the trials will receive a real treatment. There will be no use of placebos, fake drugs that produce no effect. “These patients don’t want to take placebos,” Engel said, “and most of them are probably going to be taking some of the drugs on their own anyway. If it’s (properly designed), we won’t need placebos.”
ALS affects about one in every 100,000 people, with the average age of onset about 56. It is characterized by the death of nerve cells in the brain and spinal cord that control muscle activity, producing progressive muscle weakness, paralysis and death.
The reason for this new optimism about treating what was previously an almost hopeless disease lies in the identity of the defective gene. To their surprise, researchers found that the defect occurs in the gene that serves as a blueprint for a well-known protein called superoxide dismutase or SOD1.
SOD1 is an antioxidant that “mops up” highly reactive chemicals called free radicals in cells before they can cause tissue damage. Researchers have been studying SOD1 for nearly 30 years, and the loss of its natural activity is thought to be one of the causes of aging.
Physicians hope to replace the missing SOD1 with vitamins or prescription drugs designed to mop up free radicals. Researchers will probably try a variety of combinations in hopes of determining which work best. Then they should be able to refine the treatments.
“Let’s get something that works and go from there,” Engel said.
