A bridge two-tenths of an inch long has spanned a gap measured indecades, if not millennia.
The five-millimeter link reconnected the two stumps of the spinalcords in 22 rats, transected to model repair of such injuries some dayin humans.
Neurosurgeons, neurologists and physiatrists, frustrated in efforts torehabilitate paraplegic victims of spinal cord injuries, are acclaimingthis experiment as "exciting," "a first," a "milestone," a "Holy Grail."
It's reported in the current Science, dated July 26, 1996, under thetitle "Spinal cord repair in adult paraplegic rats; Partial restoration ofhind limb function."
The paper's senior author, neurobiologist Lars Olson, at Sweden'sKarolinska Institute in Stockholm, told BioWorld Today: "We'vereplaced 18 little nerves, with precise positioning, in the rat's spinalcord, which is very small _ just a few millimeters wide. And when Isay `we,' I really mean Dr. Henrich Chang, a neurosurgeon fromTaiwan, who works with me, and he is the one who really did it.
"We have shown a principle here," Olson observed, "that it is indeedpossible to get some function back after a complete transection of anadult mammal's spinal cord. However, we have only restored a littlebit of function, and a little bit of sensory input. There are many waysin which we could improve on these results."
Chronic Injury More Typical Than Acute
He explained that in the work just published, "our attempt was to cutthe spinal cord and repair it in one and the same surgical session, tocounteract the consequences of acute spinal cord injury." The nextstep, on which he and Chang are working now, is to wait severalmonths, perhaps half a year, between cutting the cord and trying torestore it, as a model of chronic injury.
"This would better model the situation for patients," Olson said. "Wehave no results of those experiments yet."
In the U.S. alone, there are 250,000 chronic spinal-injury patients,many of whom live as long as 40 years with their disablement. RonCohen, president and CEO of Acorda Therapeutics Inc., in NewYork, told BioWorld Today that each year brings 10,000 to 12,000new cases, 90 percent of whom survive.
"Forty percent," he said, "are caused by vehicular accidents _automobiles, motorcycles, bicycles _ followed by violence, gunshotand knife wounds, then falls and sports-related trauma."
Acorda Therapeutics was co-founded in March 1995 by Cohen andneurosurgeon Wise Young, of New York University Medical Center.Young wrote an editorial accompanying Olson's paper in Science.
"Acorda," Cohen said, "is a disease-targeted company, developingnew therapeutics for spinal cord injury." It is privately held, butanticipates a new round of funding soon, probably with venturecapital input.
Besides the mechanical challenge of ultra-exquisite microsurgery,repairing the spinal cord, in rats or people, faces seeminglyinsurmountable functional hurdles.
The cord consists of an outer layer of axons sheathed in myelin _ thewhite matter, and an inner core of gray matter.
"It's known," Olson observed, "that cut nerve fibers cannotregenerate, cannot grow, in white matter. In fact, cells in white matteractively inhibit fiber growth."
On the other hand, fibers in the inner gray matter, which serve theperipheral rather than the central nervous system "actually stimulatenerve growth.
"Based on experiments that we had done 20 years earlier," Olsonrecounted, "we decided to use multiple grafts of peripheral nerves asguiding channels, as tubes, to reroute nerve channels to gray matter,where the nerves can actually regenerate."
Team To Try New Neurotrophic Factors
As struts and girders for their bridge, the Swedish team "tookreplacement fibers from nerves that run between the ribs, from thesame animal, to avoid immunological problems."
To weld these members in place, they embedded the entire repair sitein biocompatible glue derived from fibrin, and impregnated withacidic fibroblast growth factor.
"Another next step we are taking," Olson said, "is to try differentcombinations of neurotrophic factors, and whether or not to createchemical gradients of these factors along the spinal cord, to perhapsenhance their fiber growth."
In the just-reported acute injury experiments, he and Chang "studiedthe behavioral recovery in 22 rats that received the full transectiontreatment. In these animals, we saw recovery of movement in the hindlimbs, contrary to negative results in many control groups oftransected rats. And we used marker substances to demonstrate thatnerve fibers had actually grown down into the spinal cord from abovethe cut.
"But it's very important to point out," Olson emphasized, "that theseanimals were not cured, and we do not know if this is going to workin patients or not. I do not want to raise too many false positiveexpectations in people, or any hope of immediate cure. This will takemore time.
"All I can say," he concluded, "is I hope by publishing our work thatother scientists will pick up on it and help advance the field."
Accorda's Young, who pioneered early drug therapy for spinalinjury, told BioWorld Today: "The key achievement of this paper isthat it should shift the basis of the argument away from `Does thespinal cord regenerate?' to `How can we do it better?'
"It's absolutely marvelous," he added, "that somebody had thecourage to go and spend two or three years working on this. I'm surethat in 1993, when Olson started on it, there were a lot ofdisbelievers. People thought he was crazy.
"Most scientists would have said: `You can get the axons to cross thegap, but you won't get function. They got function, which tells us thatthe two major hurdles that many people think are huge mountains arereally small hills."
Young recalled that a 3,000-year-old Egyptian papyrus, published in1931, "describes spinal cord injury in soldiers, with therecommendation to not give them water; let them die."
He added that "this attitude `spinal cord injury is worse than death,'pervaded the medical field through World War II." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.