HEALING THE BROKEN SPINE

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By Joni Moths Mueller

Few researchers bring more intimate experience to the problem of traumatic spinal cord injury and

paralysis than Dr. Murray Blackmore. The assistant professor of biomedical sciences in the College of Health Sciences was 12 years old when his mother suffered a C5 injury to her spinal column. The injury near the top of the vertebral column left her paralyzed from the shoulders down. “It wasn’t an abstract problem that can happen somewhere else,” he says, remembering time spent in

rehab with his mom. Count Blackmore among the scientists who are making progress in understanding how to reverse the

injury physicians once considered untreatable. Historically, science focused on repairing the injury site. But Blackmore’s research, funded in part with a Craig H. Neilsen Foundation grant of $300,000, breaks new ground, focusing instead on re-establishing the communication highway that connects the brain and spinal cord. Neurons in the brain send signals along millions of microscopic cables that run down to the spinal cord. These cables, called axons, deliver the brain’s instructions to tell the body when and how to move. If some of the axons are damaged, those that remain will team up to restore the flow of information and most functionality. Paralysis occurs when all the axons are damaged. “You can lose 90 percent of the axons, and the remaining 10 percent is enough to carry most of the functionality,” Blackmore says. “That means if we can just get 10 percent of the cables to regrow, that is enough to make a difference.” Species such as the adult salamander are able to regenerate and regrow axons. This growth machinery is also active in the human embryo, but it’s turned off once the axons reach their target growth. “There’s an evolutionary reason for shutting down additional growth to prevent aberrant connections,” Blackmore says. “That’s nature.” He believes gene therapy can be used to reactivate the growth machinery in adult human cells. “I try to understand what is different between an embryonic neuron and an adult neuron that explains this difference in their ability to grow,” he explains. “And then — this is where it gets really cool — ultimately you want to restore that ability in the older neuron. You want to change gene expression in the older neuron to mimic the young neuron.” Blackmore’s target: the approximately 1,000 genes in the young neuron that differ from the older neuron. His lab methodically changes each gene’s expression in a petri dish. With a high-throughput screening microscope, he can see whether the gene helps axons grow and by how much. Before he arrived at Marquette, Blackmore and researchers in Miami had identified one growth-promoting gene. His Marquette lab recently succeeded with a second gene. The lab has packaged these potentially therapeutic genes in a virus and injected them into rodents with spinal cord injuries. “What we’re really excited about is we’re seeing actual regrowth of axons as a result of this gene therapy,” he says. “That’s huge. That’s a first for the field. It’s the first gene therapy reagent that can be delivered to an adult animal that can result in improved growth of a really important set of axons.” Blackmore’s findings appeared in the 2012 issue of the journal Proceedings of the National Academy of Science. Moving forward, the goal is to identify a cocktail of genes that boosts growth even more and then eventually to move to clinical trial in humans. “I

Dr. Murray Blackmore 12

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think it’s a matter of time,” Blackmore says, “but, yes, I believe we’ll have a cure.”