An experimental treatment may help slow the progression of the deadly brain disease amyotrophic lateral sclerosis (ALS), a new study finds.
Researchers called the results a promising step in the fight against a devastating and invariably fatal disease. And two advocacy groups are calling for swift action to make the drug available to patients.
ALS is also known as Lou Gehrig's disease in memory of the baseball legend who died from the disease. It's a progressive condition that kills nerve cells in the brain and spinal cord. Eventually, all muscles controlling voluntary movement become impaired, so that people lose their ability to move, talk, eat and breathe.
Most people with ALS die of respiratory failure within three to five years of their first symptoms, according to the U.S. National Institutes of Health.
There are currently two ALS medications approved in the United States. They can slow the disease course, but only marginally.
One drug, called riluzole, can extend patients' lives by an average of a few months, said Dr. Sabrina Paganoni, the lead researcher on the new trial.
That's a good thing, but clearly not enough, said Paganoni, of the Healey and AMG Center for ALS at Massachusetts General Hospital, in Boston.
So Paganoni and her colleagues tested a new medication — a combination of two existing drugs that have individually been studied for ALS. They found that when it was added to patients' standard medication, it further delayed their progression over six months.
"The benefit they found was on top of the current standard of care," said Kuldip Dave, vice president of research for the ALS Association. "That's one reason I think these results are robust."
And since the two drugs in the combination are not new, Dave said, there is already a good amount of information on their safety.
One medication — sodium phenylbutyrate — was approved in the 1990s by the U.S. Food and Drug Administration for treating a rare disorder where ammonia builds up in the body.
The other, called tauroursodeoxycholic acid, is used in some countries to treat gallstones. It's also available as a dietary supplement.
Lab research has shown that the two drugs together can protect nerve cells from death. And drugmaker Amylyx Pharmaceuticals, of Cambridge, Massachusetts, is now developing the combination as a treatment for both ALS and Alzheimer's disease.
The current trial, partly funded by Amylyx, included 137 ALS patients at 25 U.S. medical centers. Eighty-nine patients were randomly assigned to take the drug — dubbed AMX0035 — every day for 24 weeks. The other 48 patients were given a placebo (inactive treatment). All stayed with their standard medications as well.
By the end, patients on AMX0035 were doing better than placebo patients on a scale that measures physical function — such basics as walking, speaking, dressing, writing and using utensils.
On average, AMX0035 patients declined at a slower rate, for a difference of about 2.5 points on a scale of 0 to 48.
"Even that small difference can be meaningful in daily life," said Paganoni.
It could, for example, mean the difference between being able to write or not, she said.
The drug did have side effects, mostly nausea, diarrhea and abdominal pain. Those problems prompted 19% of patients to stop taking it.
The ALS Association, which also helped fund the trial, is calling for the drugmaker and the FDA to "move with urgency" to make the drug available.
The group, along with the nonprofit I AM ALS, urged Amylyx to submit an application for FDA approval — and to make AMX0035 available through the agency's "compassionate use" program until the drug comes to market.
Progress has long been hard to come by in ALS. The underlying biology of the disease is complicated, Paganoni explained, and it appears to injure nerve cells through multiple mechanisms.
And no two people with ALS are the same. "This disease is heterogeneous," Dave said. "Every person with ALS is different. Their progression is different."
The two drugs in AMX0035, Paganoni said, target two separate, basic mechanisms that kill neurons. The hope is that it will better protect the cells than current medications can on their own.
A big unknown is whether the drug can help extend ALS patients' lives. Paganoni said more answers will come soon: After this trial ended, all patients were offered AMX0035 treatment and are being followed.
Paganoni and Dave pointed to the bigger picture, as well. After years of little progress, numerous trials are testing various treatment approaches to ALS — from drugs to stem cells.
"There is hope," Paganoni said. "I'm convinced we're in a new era of ALS research."
The study was published in the Sept. 3 issue of the New England Journal of Medicine.