This is Part 1 of a two-part series.
On July 31, 2014, former college baseball player Pete Frates uploaded a 52-second video to Facebook. Frates, who has amyotrophic lateral sclerosis, bobbed his head to the tune of “Ice Ice Baby.” While he stayed dry to protect his health, Frates and his co-instigators encouraged others to dump frigid water over their heads to raise awareness, and funds, for ALS research. The result: An unprecedented amount of money started flowing into the coffers of amyotrophic lateral sclerosis charities. People from all walks of life took the plunge and sent money to various charities, supporting research on a disease many had not heard of before 2014 (see Sep 2014 news). The ice bucket challenge raised more than $220 million by summer’s end, according to the ALS Association, a U.S.-based charity that alone took in $115 million. The ALS ice bucket challenge is back this summer. Frates and co-instigator Pat Quinn headlined the kickoff event today at Fenway Park in Boston, a day after Major League Baseball announced a $100,000 donation to The ALS Association. As donors get wet again, Alzforum asks, how is 2014’s ice bucket challenge money being spent?
Different charities have taken different approaches, putting money toward care of people with ALS and their families as well as clinical trials and basic research. Some decided quickly how to spend the windfall, while others are still planning. ALS charities have been working together to share stewardship of the ice bucket challenge concept and ensure that funds are distributed wisely, said Terry Heiman-Patterson of the Drexel University College of Medicine in Philadelphia. Heiman-Patterson co-chairs the Northeast ALS Consortium and heads the ALS Hope Foundation, which netted $70,000.
The ALS Association has earmarked $77 million for research, $23 million for patient services, $10 million for public and professional education, and $5 million for fund-raising and donation processing fees. This is quite a change for an organization that normally operates on a $25 million annual budget, with about a quarter of that typically going to research. In October 2014, the association announced it would put $18.5 million toward seeding four new collaborations. ALS Accelerated Therapeutics, which aims to speed up trials, received $10 million to match $10 million from the ALS Finding a Cure Foundation. A sequencing project from the New York Genome Center received $2.5 million, matching a contribution from the Tow Foundation. The U.S. arm of an international sequencing effort, Project MinE, got off the ground with $1 million. Finally, the association offered $5 million to the Neuro Collaborative, a group of three California labs involved in several drug development projects. Those investments are seed money, and the association could offer more funding if the recipients meet milestone goals, said its chief scientist, Lucie Bruijn.
On July 14, the association announced the latest disbursements from its ice chest, with $11.6 million going to 58 new grants focused on genetics, disease mechanisms, biomarkers, drug development, and postdoctoral training. More research funding, totaling about $7.5 million, will be announced later this summer, Bruijn said. She said her board, in conjunction with peer review by experts, made funding decisions based on its goals of research, patient care, and advocacy.
The timing of the ice bucket challenge was perfect, said researchers who spoke with Alzforum. With the recent rapid-fire discoveries of new genes, and promising results from therapeutic approaches such as antisense DNA, the field was progressing and attracting interest from pharmaceutical companies, commented Clotilde Lagier-Tourenne of the University of California, San Diego (see Feb 2008 news; Sep 2011 news; Sep 2013 news story). However, scientists’ ideas were bigger than their bankrolls. Some stocked freezers full of DNA samples but had no money to sequence them; others cryopreserved patient cells that they would make into induced pluripotent stem cell (iPSC) lines if they only had the cash. Data from early stage studies of drugs languished with no backing to move ahead. With the new funding, trials are progressing, thousands of genomes are in line to be sequenced, and stem cells are morphing into motor neurons.
Once diagnosed, most people with ALS live for only a few years. Charities face enormous pressure to spend their ice bucket funds on studies that will quickly yield treatments for today’s patients. However, organizations also want to invest the one-time cash infusion wisely for the future. The ALS Association, for example, has yet to commit nearly $40 million of its planned research spending. Some researchers say that is fiscal responsibility. “You do not want to use funds on research today that could be better spent on research tomorrow,” pointed out Jonathan Katz of the Forbes Norris MDA/ALS Research & Treatment Center at the California Pacific Medical Center in San Francisco.
However, others lament the gradual pace. “I think that people are making decisions very slowly, considering the life cycle of an ALS patient,” said Steven Perrin, chief executive officer of the ALS Therapy Development Institute (ALS TDI), which rapidly earmarked its $4 million bucketful of cash for two clinical trials and a precision medicine program.
Many ALS organizations have divvied their pot to fund both research and caregiving, and some scientists wonder if that was the right move. Katz suspects donors had science in mind. “I think the right thing to do is to cure the disease with [the ice bucket money],” he said. However, the ALS Association has always been up front about patient care being part of its mission, and used some of the new money to boost its grants to multidisciplinary clinics. In recent years, the association gave each of 33 clinics a grant of $12,500 annually. It has now raised that to $25,000, and added 13 more clinics to the list. The ALS Association expects to add four more clinics by the end of 2015, said Kimberly Maginnis, chief care services officer. Many centers use the grants to hire additional staff, Maginnis said.
The U.K. Motor Neurone Disease Association, which took in a little more than £7 million ($10.8 million U.S.), and MND Australia, which received about $2.5 million Australian ($1.9 million U.S.), also have devoted funds to patient care. In fact, Australians who took the ice bucket challenge wanted exactly that. MND Australia gave contributors the choice to donate to research or to care and advocacy. “It was exactly a 50/50 split,” reported Janet Nash, the organization’s executive director for research.
Trials for Today
Even so, a substantial portion of ice bucket funding will go to speeding up the search for treatments. ALS-TDI is banking on immunotherapy with two antibodies. One is an antibody to SOD1, which misfolds and aggregates in the neurons of people with ALS. In preclinical studies, the antibody extended the lives of ALS model mice (see Apr 2013 conference news). In addition, TDI’s antibody to CD40L, a T-cell receptor ligand, delayed disease in ALS model mice and looked safe in primates, Perrin said (see Mar 2010 news). With $3 million in ice bucket funds, TDI will be able to produce enough of each antibody to get clinical studies off the ground, Perrin said.
ALS ACT also will be pushing trials forward. Merit Cudkowicz of Massachusetts General Hospital in Boston, one of the ALS ACT investigators, noted that some drugs with promising results have been stalled, waiting for funds to proceed to the next trial. The organization intends to disburse funding for up to two trials in each of the next three years.
On July 1, ALS ACT announced it would pay $3 million for trials of mexiletine and sodium chlorite. Scientists hope that mexiletine, a sodium channel blocker, will reduce hyperexcitability in motor neurons. People already take this drug to temper cardiac arrhythmia, and it proved safe for people with ALS in an earlier Phase 2 trial (Shibuya et al., 2015).
Sodium chlorite, a salt used in water purification, has already been studied as a treatment for HIV, where it seems to downregulate macrophage activity (McGrath et al., 2002). Intravenous sodium chlorite showed promising results in a Phase 2 trial for ALS back in 2012, but funding to test it further was lacking, Cudkowicz said (see Jan 2013 conference news). In addition, ALS ACT will spend some ice bucket dollars on preclinical studies of therapeutic regulatory T cells and a treatment to silence the SOD1 gene.
Ice bucket donations are fueling trials beyond U.S. borders as well. ALS Canada, which received $17 million Canadian ($13.4 million U.S.), will spend $500,000 Canadian on a nationwide study of pimozide. This inexpensive, generic antipsychotic came to Canadian scientists’ attention in a screen using a zebrafish model of ALS, said Lawrence Korngut of the University of Calgary Cumming School of Medicine, lead investigator on the trial. Pimozide, a calcium channel blocker, strengthens neuromuscular junctions. A 25-person Phase 2 trial was already in motion, and with the new money, Korngut will conduct a separate Phase 2 trial of 100 people. In the United Kingdom, the Motor Neurone Disease Association plans to contribute £500,000 (about $778,000 U.S.) to a European trial of low-dose interleukin-2, which researchers predict will promote the neuroprotective activity of T cells.
Besides these trials, ALS organizations are investing in projects they can leverage for future research.—Amber Dance
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