Cell Therapy

Bay Area researchers are using a particular cancer to produce neuronlike cells that, when injected into the brain, seem to reverse the effects of stroke. Is the treatment a historic medical breakthrough, or a reckless ploy to attract investors?

But the United States Conference of Catholic Bishops, a leading critic of stem cell research, says it has no moral objections to the science practiced by Layton, since it obtains stem cells from a tumor that merely behaves like (but is not) a human embryo.

Researchers first began studying this particular tumor in the late 1970s precisely because it behaved so much like an embryo; they were trying to determine how and why embryonic cells, which are all the same, differentiate to become skin, or heart, or kidney, or brain cells. They found, almost by accident, that this tumor's quasi-embryonic stem cells showed an astonishing determination to become part of the central nervous system. The finding surprised researchers: Teratocarcinomas usually don't display devotion to one part of the body.

More research revealed that retinoic acid, a chemical relative of vitamin A and now a common cancer treatment, acted as a kind of master switch for the tumor. The chemical not only turned off many of the stemlike cells' malignant propensity to divide endlessly; retinoic acid also caused those cells to differentiate. When scientists threw the switch, the resulting cells looked an awful lot like neurons, the cells that transmit the electrical energy of thought.

Sean Cullen: "We don't know whether this is going to work. ... But we do 
know already that it's feasible."
Anthony Pidgeon
Sean Cullen: "We don't know whether this is going to work. ... But we do know already that it's feasible."
Millions of Layton's neuronal cells are implanted into damaged areas of a 
patient's brain.
Millions of Layton's neuronal cells are implanted into damaged areas of a patient's brain.

Layton originally formed to license the manufacturing technology from the University of Pennsylvania, then patented the cells under the name LBS-Neurons (for Layton BioScience), and now stores clones of the original teratocarcinoma cells in large vats of liquid nitrogen at minus 196 degrees Celsius. In addition to treating the cells with retinoic acid, Layton also soaks them with what are known, in the jargon of cell science, as mitotic inhibitors, or drugs that kill cancer by interfering with cell division.

After about six weeks, a flask containing tumor cells holds a mixture of neuronal cells, which shine brightly under a microscope, and non-neuronal cells that, for some reason, didn't get the itch to become neurons. Using enzymes, Layton separates the neuronal cells from the others, then returns the new cells to liquid nitrogen until they're needed for a clinical trial.

"This cell has very good growth properties, probably as good as any cell I've worked with," says Michael McGrogan, Layton's vice president of research and development, who uses a PowerPoint computer presentation to explain the science. "You're not limited by pampering them."

But Layton is limited by the Food and Drug Administration, which, by all accounts, expressed a great deal of skepticism before finally allowing Layton to proceed with its study. Even then, Layton had to restrict its testing pool to patients whose strokes occurred in the basal ganglia, a set of large structures in the center of the brain that control motor function. More animal tests will be required before the study can expand to other brain sections.

The 12 patients in Layton's first clinical trial, conducted between July 1998 and March 1999, received either 2 million or 6 million neuronal cells in as many as nine different locations within the stroke-damaged area of the brain. The surgery, which lasts about four hours, is fairly simple: The patient remains awake while a frame steadies the head. Doctors drill a small hole in the top of the skull and insert a long-needled syringe into the basal ganglia.

After the cell transfusion, the doctors wait and watch while the patient undergoes two months of physical therapy to stimulate the new cells. The two-hour workouts, conducted three times a week, build dexterity, balance, and strength. It's not a complicated regimen -- opening doors, stacking cones, gripping forks, riding a stationary bike -- but if the patient doesn't attempt new exercises, the cells might not be able to help. "The study is a combination of cells and stimulation," says Dr. Alan Jacobs, Layton's former medical director, who helped design the trial. "More than just the number of cells, it's how they're administered."

In the first trial, seven patients showed substantial improvement, as measured by their own reports, doctor evaluations of their motor skills, and brain scans. Two have died of unrelated causes.

The second phase, now under way, escalates the dosage and dispenses the cells to wider areas of the brain. Six patients have already received 5 or 10 million cells, and a seventh will have surgery soon. If this phase shows progress, doctors will conduct a double-blind trial in which neither the doctors nor the patients know whether the cells, or a placebo of non-neuronal cells, are being administered.

If the double-blind trial produces improved patients, Layton will begin large-scale production, selling vials of LBS-Neurons to doctors and medical centers. Conceivably, neuronal transplantation could become the preferred treatment for stroke within five to 10 years. But Dr. Barry Hoffer, a drug and stroke expert at the National Institutes of Health, cautions that successful animal data does not always predict what works to fight stroke in humans. "On paper the science looks great, but I've seen a lot of very different, promising things not make it in the clinic," Hoffer says. "The hope is that this is not one of those."

After all, Layton's success with teratocarcinoma cells is the exception, not the rule. Even Dr. Peter Andrews, the scientist who first caused these cancer cells to differentiate by introducing them to retinoic acid in the early 1980s, points out that Layton's neuronal cells are "screwed up genetically." For some reason, they have about 60 chromosomes instead of the normal human complement of 46.

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