An experimental medication may slow the progression of amyotrophic lateral sclerosis, or ALS, researchers reported Wednesday. The research was supported in part by donations from the Ice Bucket Challenge, the social media sensation that raised more than $200 million worldwide.
The drug is not a cure, but it may help slow the inexorable disability caused by ALS, which rapidly destroys the nerve cells that control the muscles that allow us to move, speak, eat and even breathe.
"Patients keep telling me their No. 1 goal is to be able to retain physical function for as long as possible," said the study's lead author, Dr. Sabrina Paganoni, a neuromuscular specialist at Massachusetts General Hospital's Sean M. Healey & AMG Center for ALS. "They want to be able to continue to walk and to use their hands."
About 20,000 people in the U.S. have ALS at any given time, according to the ALS Association. It usually strikes between the ages of 40 and 70. Once symptoms set in, life expectancy is two to six years, on average.
The treatment studied by Paganoni and her colleagues targets two cellular structures damaged by the disease: the mitochondria, which are the cells' power plants, and the endoplasmic reticulum, the cellular dump trucks that cart away waste that can gunk up the cells' machinery.
The multicenter, randomized, double-blind study is the second step — a phase 2 trial — in a three-step process required by the Food and Drug Administration for drug approval. In a double-blind study, neither the patients nor the researchers know who is receiving the drug. If a phase 2 study generates positive results, the FDA typically requires a larger and longer phase 3 trial.
To test the effectiveness of the two-drug combination, the researchers recruited 137 ALS patients who had become symptomatic within the previous 18 months. About two-thirds of the patients (89) received the drug, while the remaining third were given a placebo.
Participants were evaluated on a scale of 0 to 48, measuring the disabilities caused by the disease.
"By the time they entered the trial, on average, patients had already lost 12 points. Their baseline score was about 36, on average," Paganoni said. "Each question addresses a specific domain of function and is scored on a scale from zero to four."
For example, for walking:
4 = Normal
3 = Early ambulation difficulties
2 = Walks with assistance
1 = Nonambulatory functional movement only
0 = No purposeful leg movement
During the six months of the study, patients taking the medication lost an average of 2.32 points less than those receiving placebos, a 25 percent better functional outcome.
"A 2- to 3-point change can mean the difference between being able to do an activity independently or with an assistance device," Paganoni said.
The trial did not show a difference between medication and placebo in outcomes such as time to death, tracheostomy, or permanent intubation, or hospitalization. But that may be because it ran for just six months.
Paganoni suspects that, if it is approved, the new drug would be just one part of a cocktail of medications that would help to keep ALS at bay.
Because the trial showed that the medication might make a difference, all participants were offered the opportunity to stay on it or, in the cases of those who were given placebos, to start on it. The Mass General researchers will track how the patients taking the medication do in the long term.
Paganoni credited the Ice Bucket Challenge for getting her study and others going.
"The Ice Bucket Challenge was an important turning point in the fight against ALS," she said. "It put ALS on the map and raised awareness of the disease and attracted more investigators and investment to the research."
With the good news from the trial, the ALS Association hopes to persuade the FDA to allow other patients to have access to the drug, even before phase 3 trial results are available.
"It's very unusual for an ALS clinical trial to hit its primary endpoint, so we're very excited about it," said Neil Thakur, chief mission officer for the ALS Association. "It's the difference between being able to feed oneself versus being fed or needing versus not needing a wheelchair."
ALS experts cautioned against rushing ahead without more data.
"The current data are definitely positive, but they need to be replicated," said Dr. Martina Wiedau-Pazos, a neurologist who is director of the ALS Clinic and Research Center at UCLA. "This study has limitations, such as being small and lasting just six months. I think a phase 3 trial is needed, because, in the past, positive outcomes from phase 2 trials were not confirmed in phase 3 trials."
Another issue is that the study included subjects who had more rapid disease progression than normal, said Dr. David Lacomis, chief of the neuromuscular division at UPMC in Pittsburgh. "So it's unclear what the effects would be in the broader ALS population," Lacomis said via email.
While the new findings are promising, they are not "earth shattering," said Dr. Erik Pioro, director of the section of amyotrophic lateral sclerosis and related disorders at the Cleveland Clinic. "But it does add credence to the idea that other pathways are playing significant roles in ALS pathogenesis."
Results of the trial were published in the New England Journal of Medicine.