Spinal trauma sees hope

WEST LAFAYETTE, IND. — A liquid polymer can prevent paralysis after serious spinal injury if it is injected into the effected area within 72 hours. The procedure, which will be presented to the U.S. Food and Drug Administration (FDA) for approval in human trials during the next 18 months, showed efficacy in about 75 percent of canine subjects.

Researchers at the Center for Paralysis Research in Purdue University's School of Veterinary Medicine developed the treatment process, which uses polyethylene glycol (PEG) to prevent nerve cells from rupturing irrevocably, thus allowing the spinal cord to heal itself.

"This stuff is a miracle for the dogs," says Richard Borgens, PhD, director of Purdue's Center for Paralysis Research. "Researchers typically only look at deep pain as an index of how badly injured an animal is. For a dog to be enrolled in our studies, they must be zero on every single thing that we measure, so we get the very worst of the worst. Of those dogs, only about 17 to 20 percent will have any form of quality of life after six months. PEG injections reverse that proportion, so about 78 to 80 percent have fully functional lives. They are continent again; they're walking again. Some have some coordination issues, but you cannot tell that many of them were ever hurt."

The substance works by forming a film over the area of damaged membranes, nerves and other cells, and it forms a seal, Borgens explains. Therefore, the hole or the breach in the membrane cannot enlarge, and it allows the nerve to function immediately.

"After it seals the hole, the membrane beneath it reconstitutes itself spontaneously, and that's why only two injections are required (before and after surgery)," Borgens says. "It's totally safe; it's been used in medicine a long time."

The PEG study began almost five years ago with guinea pigs and rats before it moved to dogs. The canine study treated 19 paraplegics with PEG and standard treatment, which included steroid injections, physical therapy and surgical removal of any offending chips. The 24 subjects in the control group received only standard treatment. The dogs' improvements were measured based on desire to move, deep and superficial pain perception and transmission of electrical impulses through the nerve tissue. More than half of the dogs in the PEG group were standing or walking within two weeks, and many showed positive signs within three to five days, Borgens says. Almost 75 percent resumed a normal life after six months.

The research was performed at Purdue, Indiana University-Purdue University, Indianapolis; and Texas A&M University.

"We know it's extremely important for dogs in the early phases of an acute neurological injury to get an injection (of PEG). It's sophisticated in the way that it works, but it's not sophisticated in terms of how you apply it. It's simply an IV injection," Borgens says. "An average practitioner would be able to do this, but in most cases of severe neuroinjury, there is going to require surgery. This is not to replace surgery; it provides a good quality of life and a recovery to functional status for the animal that requires surgery, too."

Barriers to entry

Despite its promising success, it likely will be several years before general practitioners have access to the materials used in the procedure, Borgens says. Purdue buys PEG in bulk from a chemical supplier and then alters it to meet specific medical needs.

"Polyethylene glycol is a common substance, but getting it at the right concentration and as a sterile solution for injection in a clinical setting requires effort," he says. "One day, hopefully not too many years from now, it might be marketed by a company that will provide injectable solutions that can be used in severely-injured animals."

The FDA approval process can be a time-consuming hurdle, too. It's difficult for clinicians to obtain approval and access for materials and procedures that already have proven to be safe and efficacious in animal injury and disease, Borgens says.

"Years later when it is approved for human medicine, then veterinarians get to prescribe it or use it, and that doesn't make sense to me because there is a branch at the FDA that is involved with animal medicine," he says.

The process isn't a panacea for neurotrauma, either, Borgens warns. PEG is intended for use during the first 72 hours of an injury. Otherwise, it's unlikely the process will work.

"Spinal cord injuries and head injuries are extremely complicated, and the idea that there is going to be one magic bullet to put Jack back together again is silly," he says.

Purdue currently is collaborating with Iowa State University's School of Veterinary Medicine to streamline its clinical story for FDA review. The proposed study already has received comments from an Institutional Review Board (IRB), an FDA task force designed to review and monitor biomedical research involving human subjects. An IRB has the authority to approve, disapprove or require modifications to research protocols before human studies can advance.