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After Ice Bucket campaign, researchers have optimism about insights into ALS puzzle

08/12/2014 CHELSEA, MA Staff members participate in the ice bucket challenge at The Leonard Florence Center for Living (cq) in Chelsea. (Aram Boghosian for The Boston Globe)Aram Boghosian for The Boston Gl

Five years after Pete Frates helped launch the Ice Bucket Challenge to raise awareness and money for ALS research, a surprising adjective describes the feelings of researchers studying the fatal disease, which relentlessly destroys the ability to move.

That word? Optimistic.

Dr. Merit Cudkowicz of Massachusetts General Hospital put it this way: “I really think we’re going to have new treatments in 2020.”

Said Dr. Robert H. Brown Jr. of the University of Massachusetts Medical School: “It’s a phenomenally exciting time.”

Since Frates launched his campaign, new insights into the biology of ALS have led to the development of more than a dozen potential treatments. Cambridge-based Biogen has four ALS drugs under study, for example.


Of course, the rocky shoreline of science is littered with researchers’ shattered hopes. There is currently no cure for ALS, and only time will tell whether the drugs under investigation turn out to work.

But Frates, a former Boston College baseball star who died of ALS on Monday, brought international attention to the disease at an especially opportune moment, said Cudkowicz, director of Mass. General’s Sean M. Healey & AMG Center for ALS.

The research community, she said, was ripe for the infusion of cash and attention his fund-raising campaign brought.

“The science was really getting exciting five years ago, but there was little funding for it,” Cudkowicz said. “Then all of a sudden, there was this huge explosion of funding but also awareness.”

That boosted ongoing research and also attracted the attention of neuroscientists and specialists in other neurodegenerative diseases, who decided to include ALS in their research and soon discovered commonalities.

ALS, or amyotrophic lateral sclerosis, destroys the nerve cells controlling movement, gradually depriving its victims of the ability to walk, talk, eat, swallow, and eventually breathe. The lifetime risk of getting ALS is 1 in 300 for men and 1 in 400 for women. Just over 5,000 people are diagnosed with ALS in the United States each year.


FDA-approved drugs can slow its progression or treat some of its symptoms, but so far there is no treatment that stops ALS.

But these optimistic researchers expect that to change soon.

The first beneficiaries are likely to be those who have a form of ALS caused by an inherited gene mutation, only about 10 percent of ALS patients. The culprit genes have been identified, and drugs that will silence two of the most common mutations are in clinical trials.

But for the more common forms of ALS, the cause is obscure — and maybe there’s more than one. Certain athletes and military veterans are slightly more likely to get ALS, but no strong risk factors have been identified. “There’s no smoking gun,” Cudkowicz said.

Unable to pinpoint a cause, researchers have focused on understanding the process that kills the motor neurons. Several possible pathways are under study, including inflammation, misfolded proteins, and malfunctions in structures within cells.

“We didn’t know most of this five or six years ago,” Cudkowicz said. “The science is just exploding. The sheer number of people working on this is going up exponentially.”

It’s possible that the mechanism differs from person to person, or that a variety of mechanisms work in concert. “Is ALS one disease or is it hundreds of diseases?” she said.

The ALS Association’s research program has tripled since the Ice Bucket Challenge started in 2014, said Neil Thakur, the association’s executive vice president for mission strategy, expanding from $4 million to $6 million in 2014 to $17 million today.


The association provides seed funding for researchers to test out an idea; when they have data showing promise, they then apply for larger grants, primarily from the National Institutes of Health.

“We’ve been able to encourage a lot of collaboration among ALS scientists,” Thakur added. “And more people are working in ALS.”

The expansion of research and new investments by biotech and pharmaceutical companies “leaves us in a really optimistic state right now where we think we may be at the cusp of a breakthrough,” said Kuldip Dave, the ALS Association’s vice president for research. Several clinical trials in their final stages are expected to end next year. If the results are positive, Dave said, “It’s possible we may have new therapies, especially against genetic targets, over the next couple of years.”

While the greatest advances have been made in the genetic type of ALS, that research has spilled over into understanding the more common forms of ALS, said Brown, UMass professor of neurology and a long-time ALS researcher.

Brown described the disease with the metaphor of dominoes falling. In the genetic form of ALS, a gene mutation starts the cascade, and identifying that mutation has helped understand what happens as the dominoes topple. With the more common forms of ALS, an unknown factor knocks down the first domino, but the rest of the process is similar. Knowing how the dominoes fall can help find targets for treatments for all forms of ALS.


This progress reflects what Daniel L. Doctoroff — founder of Target ALS, a nonprofit research foundation — calls “a virtuous cycle”: More money leads to scientific advances, which attract the growing interest of biotech and pharmaceutical companies, which in turn spawns more interest by researchers to pursue further advances.

Six years ago, when Target ALS held its first annual meeting, six biotech companies showed up. At the last annual meeting in May, 94 came.

“ALS is actually one of the most promising and exciting diseases to work on in neuroscience,” said Doctoroff, a technology executive whose father and uncle died of ALS. Researchers are starting to see commonalities between ALS and other neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s, and fronto-temporal dementia.

Will any of this work come to fruition in time to help people currently living with ALS? Brown, the UMass researcher, thinks it could happen.

“There’s clearly something coming down the pike. Whether it will get to people who have the disease today — there is reason to be hopeful,” Brown said. “No question about that.”

Cudkowicz, of Mass. General, agreed. “People living today can have hope that something be developed in their lifetime that will at least slow down the illness,” she said.

Meanwhile, Cudkowicz said, Frates’s work has energized a powerful community. “There are so many people doing so much lobbying at the FDA, lobbying the government for money,” she said. “It’s an amazing community of patients and family members and doctors trying to defeat this awful disease.”


Felice J. Freyer can be reached at

Correction: An earlier version of this story gave an incorrect title and affiliation for Dr. Robert H. Brown Jr. He is professor of neurology at the University of Massachusetts Medical School.