Nerve transplant: proceed with caution.

Nerve transplant: Proceed with caution

The use of transplanted nerve and brain tissue to cureneurological disorders has exciting clinical implications for treatment of illnesses such as Alzheimer's disease. But so many questions remain regarding their effectiveness and ethical issues that experimentation must proceed carefully, cautioned researchers gathered last week for a symposium at the annual meeting in Chicago.

Albert J. Aguayo of McGill University in Montreal emphasizesthat nearly all neural transplant work thus far has been "pure experimental work. As far as I'm concerned, the applications . . . are far away from being directly relevant to clinical work.' Aguayo and his co-workers have succeeded in connecting the end of severed optic nerves in rats to parts of the brain, using "bridges' of nerve from the peripheral nervous system--in this case the sciatic nerve of the leg (SN: 3/29/86, p.204). Long fibers, called axons, will grow fron the eye along this bridge to the brain, reconnecting with cells in the brain.

In fish and amphibians, this nerve regrowth can actuallyrestore sight. But complete restoration of function has yet to be demonstrated in the mammalian system, says Aguayo. However, he adds that, in more recent work by the McGill group, the measurement of electrical signals from regrown optic nerve fibers suggests that "some of these [cut] axons . . . are still capable of either retaining or regaining some of their normal function.' Whether the observed "rewiring' will be sufficient to actually restore sight remains unanswered.

Another symposium participant, Victoria N. Luine of NewYork's Rockefeller University, reports that fetal brain cell transplants can restore normal sexual activity in laboratory rats, who exhibit abnormal sexual responses following the experimental destruction of certain areas of the brain controlling such behavior. Results of the study illustrate a troubling aspect of neural transplantation that is attracting attention among transplantation researchers. Ten weeks after transplantation, the graft apparently has lost its effectiveness, although the cells and their fibers remain in place.

This so-called "run-down' is being observed in other neuraltransplant systems, according to symposium organizer Roger M. Morrell of the Neuroscience Research Foundation in Southfield, Mich. A similar loss of beneficial effects was seen in the only known nerve transplantation work done in humans, reported in 1985 by a group of Swedish researchers.

"Almost all grafts run down after some time, through areaction that does not seem to be the same thing as graft rejection (a type of immune response mounted by the host against the graft),' Morrell says. The cause of this loss of function--which would severely limit the usefulness of any graft procedure--remains a mystery. But an article in the Feb. 13 SCIENCE by Jeffrey M. Rosenstein at George Washington University in Washington, D.C., may provide a clue.

Rosenstein reports that transplants from fetal central nervoustissue have "permanent barrier dysfunction,' which means that compounds carried in the blood can cross the blood-brain barrier. The barrier normally is very selective about which substances enter the brain (SN: 1/31/87, p.68). This "hole' caused by the graft exposes the entire brain to potentially deleterious agents.

It also exposes the field of neural transplants to morepossibilities, according to Fred H. Gage from the University of California in San Diego. "[Rosenstein's report] opens up a new door for us [in terms of transplant study],' he says.

Despite the uncertainties and the controversy surroundingthe Swedish study, Morrell predicts that neural transplantation studies will be conducted in human subjects within the next three or five years. Still, clinicians and researchers will have to dig deeper and ask some tough questions about risk versus benefit, says Gage, who points out that "in a sense, the cream has been wiped off the top of the neurotransplant field.'