Remember six years ago when everyone from celebrities to your next door neighbor was dumping buckets of ice over their heads and then challenging others to do the same? The so-called Ice Bucket Challenge raised awareness and over $200 million for amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease. But did all that money really help the cause? The results from two recent clinical trials at Massachusetts General Hospital indicate a resounding yes.
The findings from the trials, conducted by investigators at the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, demonstrate that an experimental medication—manufactured by Amylyx Pharmaceuticals, Inc.—not only slows the progress of ALS but also has the potential to prolong patient survival.
"The Ice Bucket Challenge was an important turning point in the fight against ALS," said Sabrina Paganoni, MD, investigator at the Healey & AMG Center for ALS and co-author of the studies. "It put ALS on the map and raised awareness of the disease and attracted more investigators and investment to the research."
The initial Phase II trial, which recruited its first participant in June 2017 and concluded in November 2019, enrolled 137 patients with ALS to receive the experimental AMX0035 medication or a placebo. AMX0035 is a combination of two drugs—sodium phenylbutyrate and taurursodiol—that each target a different cell component important for protecting
According to the study, over six months, patients who were treated with AMX0035 had better functional outcomes than those treated with a placebo, as measured by the ALS Functional Rating Scale (ALSFRS). ALSFRS is a questionnaire that evaluates several activities of daily living, such as a patient’s speech, handwriting, dressing and hygiene, walking, breathing and more. The scale operates on a numerical slide from 4 to 0—with 4 being fully functional and 0 being complete loss of function.
The walking measure, for example, looks like this:
4—Normal
3—Early ambulation difficulties
2—Walks with assistance
1—Non-ambulatory functional movement only
0—No purposeful leg movement.
At the end of six months, the patients who received AMX0035 lost an average of 2.32 points less than those who received a placebo. This equates to a 25 percent better functional outcome.
Given these positive results, which Paganoni described as “a milestone in the fight against ALS,” the research team invited all study patients to also participate in an Open Label Extension trail to assess the medication’s long-term impact.
Examining 135 of the original 137 patients enrolled in the CENTAUR study, the research team found that those who were randomized to receive AMX0035 lived for a median of 6.5 months longer than those originally randomized to receive the placebo.
“These findings are an important step forward because, in this trial, early treatment with AMX0035 was associated with longer survival in people with ALS,” said Paganoni. “These results provide substantial evidence supporting the role of AMX0035 for the treatment of ALS. Next steps will depend on ongoing discussions with regulatory agencies.”
A former Boston College baseball player named Peter Frates was the inspiration behind the Ice Bucket Challenge that swept social media. Frates, who was diagnosed with ALS in 2012, had initially championed the challenge as a way to raise awareness of the neurodegenerative disease—but it went way beyond that. Ultimately, more than 17 million people participated in the challenge, with over $200 million raised from 2.5 million donors. Frates succumbed to ALS in December 2019 at the age of 34.
Photo credit: The ALS Association