HOUSE_OVERSIGHT_015495.jpg

NAUTIL.US | TEXT SETS

really strange gene mutation that was completely inexplicable." She says it has been a hard disease to study, partially because the implicated protein is unstable and partially because it was a rarity among the orphan diseases. When it comes to funding, calpainopathy has been overshadowed by other forms of muscular dystrophy. "Muscle studies have been underfunded forever and certainly a rare disease like 2a especially underfunded," Spencer says.

In 2010, Wrubel formed the nonprofit Coalition to Cure Calpain 3. In the quest for a cure, she says, "It's a matter of patients taking charge of their diagnosis." She reached out to other sufferers via Facebook, and some donated money. She partnered up with two other nonprofits that had raised funds on their own, both started by those afflicted with Type 2a. So far Wrubel's efforts have gathered close to half a million dollars. With that money, she has funded a project with Louis Kunkel, professor of genetics and pediatrics at Boston Children's Hospital, one of the nation's key muscular dystrophy researchers.

Her coalition also organized a conference to bring calpainopathy researchers together, including Spencer. Years earlier, in 2005, Spencer made a significant breakthrough. She discovered that calpainopathy, unlike more common forms of muscular dystrophy, was not a weakening of the muscle but a growth problem—muscle forms, but fails to grow because of a missing protein. It is different from other muscular dystrophies in which the lack of the protein complex, dystrophin, damages muscle membranes. "With calpainopathy, the muscles lack the growth signal," she says. "It's not transmitted properly." That difference makes a drug cure more possible. "I think this is going to be the easiest muscular dystrophy to cure," she says.

Encouraged by the promise, the Coalition to Cure Calpain 3 gave Spencer's lab a $260,000 grant to investigate how to circumvent the signaling problem and come up with a drug to fix it. But because the United States Food and Drug Administration already has a library of approved compounds that stimulate cell growth in muscle, Spencer's team may arrive at a solution sooner. With the help of the coalition's money, her lab is now plowing through the thousands of existing compounds, choosing those fit for testing. "I think it will be five years before we start thinking about clinical trials," Spencer says—and then another five years before the drugs can be commercially available, she estimates.

Wrubel's coalition intends to get pharmaceutical companies interested, too. "Many pharmaceutical companies see treating orphan diseases as a way to increase profits," Wrubel says. Her husband, Lee, adds, "The whole model for big pharmaceutical companies going forward is different. There is too little in the big pharmaceutical pipeline, and they're looking to feed that beast as much as possible." A 2012 Thomson Reuters study found that drug companies stand to profit from orphan drugs because, compared to drugs for common afflictions, they often have shorter and less expensive clinical trials, with more success. Spencer says a drug for calpainopathy, for instance, would also be useful for patients with Lou Gehrig's Disease and bed rest patients, as it would help arrest the loss of bone and muscle mass. Wrubel hopes to bring Cydan Development, a venture-capital backed orphan drug developer, to their upcoming fall conference in the Netherlands.

As for the Topics, they were excited to learn about Wrubel from Nautilus. Ivana recently connected with Wrubel through Facebook. "I only talked with her a little bit, but she seems ambitious and driven," Ivana says. "Definitely not someone who is going to sit around and wait for something to happen. Definitely inspiring. And the possibility that something might help in any way is a good thing to hear, for sure." Ivana says she now wants to get involved and advocate for her own disease. "I definitely want to do something," she says, and Wrubel's coalition "would be a good place to start." @

jude isabella is a science writer based in Victoria, British Columbia. Her new book, Salmon, A Scientific Memoir, will be released next year.

35

HOUSE_OVERSIGHT_015495