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Until now, the funding landscape for is determining the disease mechanism—and amyotrophic lateral sclerosis (ALS) has the funding for that is limited,” Cleveland been dominated mainly by the US National says. Currently, whole-genome sequencing Institutes of Health (NIH), which provided costs approximately $1,200 per patient, over $39 million last year for projects to making the cost for large-scale studies to develop animal models, study genetic risk identify genetic and environmental risk factors and test new therapies involving stem factors prohibitive. Large-scale genome- cells. But as Nature Medicine went to press, wide association studies haven’t been done a social media phenomenon known as the adequately in ALS, says Bryan Traynor, a Ice Bucket Challenge had raised more than neurologist at the US National Institute on $100 million toward solutions and increased Aging, who led the team that discovered the awareness for this progressive and fatal C9ORF72 repeat in ALS. “If we have large neuromuscular disease that affects about amounts of money, we should definitely be 5 in every 100,000 people worldwide (see going after genome-wide association studies Editorial, page 1079). [and] genome and exome sequencing studies The $100 million gained this summer by that will help dissect the architecture of the the Washington, DC–based Amyotrophic disorder.” With the new funds, Bruijn wants Lateral Sclerosis Association (ALSA), is more to get more people from industry interested than 35 times the funds it received last year in finding genetic markers for the disease: in July and August. And although the ALSA, “biomarkers is an area where we want to which historically spends approximately 28% develop a competitive landscape for the of its funds on research, has not made its i n du s t r y.” plans for spending these funds public yet, the copyright Dong Hyun Kim The previously unavailable extensive scientific community has a few ideas ready. Challenge accepted: Cleveland's lab splashes out. funds have also allowed ALSA to consider Many scientists have pointed to genetic undertaking large-scale projects such as Nature America, Inc. All rights reserved. America, Inc. © 201 4 Nature therapies that might work for the disorder. building patient repositories of genetic Multiple gene mutations have been the giants of the pharmaceutical industry material that are more comprehensive that implicated in ALS. However, SOD1, the first have not shown much interest so far in early- the current ones, which was previously too npg gene linked to the disorder, and C9ORF72, a stage ALS trials, which can be expensive. He expensive. Orla Hardiman, director of the gene affected in familial ALS as well as some now hopes that the new funds from the Ice National ALS Clinic in Dublin and the Irish sporadic cases of the disorder, are currently Bucket Challenge will fuel phase 1 research ALS Research Group, says that building such the main focus of drug developers. Recently of genetic therapies. collections now, as well as building patient a phase 1 clinical trial, funded by Isis registries, would lay a stronger foundation Pharmaceuticals of California, demonstrated Getting pharma involved for future clinical trials. the safety of an antisense oligonucleotide The ALSA is now considering new types “One of the ways to utilize resources raised designed to silence an errant version of the of mechanisms to involve pharmaceutical by the Ice Bucket Challenge would be to put SOD1 gene in 32 patients with ALS who had companies more directly with ALS drug a more robust footing for the resourcing this type of genetic abnormality. The clinical development. of population-based longitudinal [patient] trial was a gamble in that it delivered the “One of things we are most interested in is registries, so they are adequately funded till therapy into the central nervous system. to accelerate the early stage of de-risking perpetuity, so that patients can be tracked,” “Getting the therapy to the clinical trials clinical therapies,” says Lucie Bruijn, the she says. was very difficult,” says Don Cleveland, chief scientist at ALSA, who has been a major The Ice Bucket Challenge has produced a neurobiologist at the University of figure in directing the research agenda of the more cash for ALS advocacy and research California, San Diego School of Medicine, association. She points to the partnership groups beyond US borders. For example, whose lab was a part of the group that between Isis Pharmaceuticals and research ALS Canada has raised more than C$14 conducted the early research in developing labs for the development of SOD1 antisense million ($12 million) and the Irish Motor the antisense technology targeting SOD1. technology as a model that the ALSA might Neurone Disease Association has received Cleveland, who did not study the therapy support in the future. €1.4 million ($1.8 million). The coming in humans, notes the clinical trial received Despite a number of genetic studies on months will be a test of spending it wisely. funding from the NIH and the ALSA, but ALS in the last decade, “the biggest challenge Manasi Vaidya

1080 VOLUME 20 | NUMBER 10 | OCTOBER 2014 NATURE MEDICINE