April 21, 2010 -- Victims of severe spinal injuries may someday be able to avoid paralysis if given a treatment targeting their genes in the hours after they are hurt, according to a new study released today.
Working with lab mice, researchers administered a drug that shut off a gene also found in humans that kicks in following a spinal injury. This gene has been linked to the damage that causes paralysis in people following damage to the spinal cord. By shutting it off, researchers were able to preserve function in the mice, showing that mice treated after injury had one-third to one-fourth of the damage that untreated mice did.
"There's real hope that a very simple drug that's easy to manufacture and should be well tolerated... could be given to patients with acute spinal injury," said Dr. Marc Simard, a professor of neurosurgery at the University of Maryland School of Medicine and one of the study's authors.
He said that the approach, if successful, could allow doctors to pinpoint treatment to a specific area.
The new therapy targets the gene Abcc8, which prevents cells from being overwhelmed by an influx of calcium in the body. Typically, this is helpful. However, following a spinal injury, this response is triggered and allows the cells to keep out calcium, but also to be overwhelmed with sodium, killing the cells.
The effects of that cell death ultimately can lead to paralysis.
"There's really hope -- the way there has not been hope in forever," Simard said.
The research appears in the most recent issue of Science Translational Medicine.
"It's very novel, it's very exciting, and our greatest hope is the investigators will continue to pursue this to some translation, which I realize is a tall order," said Susan Howley, executive vice president of research for the Christopher and Dana Reeve Foundation, which gave partial financial support to the research.
"It's certainly worth going down every pathway and exploring it, because what the next guy finds might be a real improvement on what's currently out there," Howley said, noting that the gene therapy in the current study is one of several avenues being explored for spine injury.
Howley said that while the results in mice are encouraging, clinical trials in humans will take time and moving this research to treatment in people could take 12 to 20 years.
"The more we can educate people and set reasonable expectations, the better off everyone is," said Howley.
A Need For Multiple Options
Perhaps the most recent public example of potential benefits from immediate spinal treatment came when National Football League tight end Kevin Everett of the Buffalo Bills was injured in a game on Sept. 9, 2007. He was quickly treated with cooling therapy on his spine and has defied expectations at the time by walking again, although his football playing career ended with the injury.
Cooling therapy, while promising, has not become the standard of care for immediate treatment of severe spinal injuries.
"It is still certainly in need of a rigorous clinical trial investigation as to whether or not it is actually safe and efficacious," said Howley. "There is a natural course of recovery that occurs without any kind of extraordinary therapeutic intervention, which is a good thing because we don't have any right now."
And cooling therapy may be just part of treatments needed to help someone with severe spinal injury make a full recovery.
"As a neurosurgeon, I would say it would require a multidisciplinary approach," said Dr. Jason Huang of the University of Rochester Medical Center.
Huang said that ultimately therapy would probably include some surgery and other interventions immediately after injury, rehabilitation afterward, and possibly stem cell therapy in the end stages of treatment.
"I think you need a multiple team approach, not just one single one, but this could be a very exciting one," he said.
Clinical Trial for Paralysis Shot Still Far Off
Noting that the current research was following up on earlier findings from the same investigators about the course of paralysis following spinal injury, Huang said, "It's not a breakthrough investigation, but it's definitely an important one along that line of investigation."
But, he added, "I think there's still a way to go for a clinical trial."
In addition to having another lab replicate the study's findings, Huang explained that researchers would need to determine dosage of a drug and the window in which it would need to be given following spinal injury.
"It's a very long road," Howley agreed. "It's not a breezy pathway, by any means."
But, she added, "We'll look forward to what we're going to hear from these investigators in the future."