Published On March 12, 2015
THE LATE SUMMER OF 2014 WILL BE REMEMBERED AS THE DAYS OF THE BUCKET. The fundraising challenge—douse yourself with ice water and post it on Facebook—introduced millions of Americans to amyotrophic lateral sclerosis (ALS), a rare neurological disease that gradually strips the body of its ability to move. By the thousands, people doused themselves to spur awareness of ALS and to raise funds to fight it.
With fewer than 6,000 new cases of ALS diagnosed in the United States each year, advocates were unprepared for the sudden windfall of resources and interest. But leading research teams quickly aligned their priorities and worked to share resources across institutions. Now, many months after the Ice Bucket Challenge, the science made possible by a thousand dunks is beginning to take shape.
The ALS Association received more than $100 million in donations in just one month last summer—compared with about $3 million during the same period the previous year—and it plans to triple its funding for research. “This money allows the field to tackle some of the biggest problems we’ve known about but haven’t had the funds to address,” says Merit Cudkowicz, chief of neurology at Massachusetts General Hospital. (Cudkowicz has another reason to be happy about the Ice Bucket challenge; one of her patients is Pete Frates, the former Boston College baseball captain who helped launch the idea.)
Yet the challenges of ALS are daunting. It’s a progressive and ultimately fatal disease that attacks nerve cells in the brain and spinal cord that control movement. As cells waste away, patients become paralyzed and eventually lose the ability to swallow or breathe. While a few people live with ALS for decades, most survive for just a few years after their diagnosis. Current treatments are limited, the disease has no cure and many questions linger about its cause.
In October, the ALS Association announced an initial commitment of $21.7 million toward new research efforts, which will be split among four large collaborative projects. Cudkowicz is a lead investigator of the largest of these, called ALS Accelerated Therapeutics (ALS ACT), which is jointly funded by a new ALS foundation called ALS Finding a Cure and the ALS Association. ALS ACT is a collaboration between General Electric (GE) Healthcare and four academic centers in the Northeast ALS Consortium, a network of researchers who run ALS clinical trials.
ALS ACT will tackle key barriers that hinder ALS drug development, including the lack of a biomarker that signals the presence of ALS. Currently, Cudkowicz says, it takes on average a year to get an ALS diagnosis after first experiencing symptoms, in part because of the lack of a specific test for the disease. Clinicians need an objective measure of the disease so that they can diagnose it earlier, track patients’ progress over time and evaluate how well experimental treatments are working. Preliminary research suggests that visible changes in a brain region controlling movement, visible on a brain-imaging scan, might serve as such a biomarker. The ALS ACT team will use GE’s MRI and PET imaging technology to test this hypothesis by imaging the brains and tracking how symptoms progress in people with ALS compared to healthy controls. The ALS ACT team will also support preclinical work to develop additional imaging and fluid based biomarkers for ALS.
The initiative will also fund clinical trials for promising treatments ready for people with ALS today. These include gene therapy to correct a mutation that causes some cases of ALS, and an immune therapy approach. Two trials are planned so far, and the ALS ACT team has put out a call for additional ideas worthy of testing in patients.
A key goal for the new research funding is to build strength in numbers. Because relatively few patients have ALS, researchers need to work together to collect the large amounts of data and clinical samples they need. To that end, the ALS ACT team will join forces with other newly funded projects, including two that will focus on genetics. Science has already uncovered genetic mutations that cause a small percentage of ALS cases, but that leaves a majority of cases with no known genetic cause. Scientists hope that by analyzing the genomes of larger numbers of ALS patients, they will identify rare or subtle genetic changes that contribute to the disease.
Genetic findings could, in turn, lead to a better understanding of the disease’s causes and help in the design of new drugs. The New York Genome Center, a consortium of several institutions, will sequence genomes of ALS patients and serve as a repository for data about ALS genetics. An international collaboration called Project MinE will use thousands of patient samples to hunt for rare genetic changes that distinguish ALS patients from people without the disease.
In addition, three California-based ALS research labs have joined forces to form the Neuro Collaborative, which will create induced pluripotent stem (iPS) cell lines from ALS patients that can be used to screen for new drugs and will be shared with the other groups.
This surge of ALS research may also offer insights into one of the disease’s most puzzling quirks: Why does ALS progress so differently in different people? While genetic analysis has started to untangle some of the reasons, what’s really needed is to study thousands of patients in great detail. Funding from the Ice Bucket Challenge will allow just that. By sharing imaging, genetic analysis and iPS cells, researchers can start “deep phenotyping”—or finding ways to distinguish one sufferer of this debilitating disease from another.
Cudkowicz and her colleagues hope that with new resources, they can get tangible results quickly. They owe it to patients such as Frates, she says, and to all the thousands of others who took notice of ALS and pledged themselves to help.
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