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November 17, 2009, 8:55 AM
Hans Keirstead Can Make Mice Walk Again (and Humans, Too?)

Seven years ago, he used stem cells to make paralyzed rats walk again. Next year his stem cell elixir will be injected into humans. What's next? It's anyone's guess.

By M.A. Woodbury

In 2002, at his lab at UC-Irvine, Hans Keirstead delicately sliced open the spines of eight lab rats with a scalpel, then not so delicately punched into their spinal-cord tissue with the force of two hundred kilodynes. A week later, he reached for a vial inside which was something most of the scientific world believed was impossible: a stem-cell solution so pure that the risk of any newly derived nerve cells morphing into tumors had been all but eliminated. He drew some liquid from the vial and injected his elixir — set to grow into oligodendrocytes, which help ferry movement-generating electric impulses into muscles — into the spines of the recently paralyzed rats. Then an assistant grabbed a camera. The resulting video was short, but its meaning was unmistakable: The rats stood up and wobbly walked. The clip went viral and the public cheered. But many of Keirstead's colleagues were less sanguine. Was the science right? they wondered. He hadn't even published a paper on it yet. As early as this spring, we'll begin to find out.

Pending one final review, next year a handful of paralyzed men and women are set to get Keirstead's high-purity stem cells injected directly into their spinal cords, above and below the injury site. Conducted by the Geron Corporation — to whom Keirstead turned over his research — it will be the first-ever test of purified stem cells in humans. Again, the public is mesmerized by what could happen, and again, Keirstead's colleagues are nervous. If the phase-one trial exacerbates a subject's condition or, far worse, kills one, Keirstead's test won't just fail, it could retard progress on stem cells for decades. He is in effect taking the first major step on stem cells for everyone. And he's doing it with a novel therapy that has a shorter paper trail than most.

Aware of the stakes, the FDA temporarily put the brakes on the trial in August, weeks before it was originally set to begin, so it could rereview the data. But Keirstead is unfazed. He has confidence in his work. The trial application Geron submitted was the longest ever — twenty-two thousand pages — all pointing toward the success and efficacy of Keirstead's method. He feels certain the trial will go forward. "My guess is that the FDA got new supporting data that is very interesting and they just need time to vet it."

But Keirstead says he doesn't have time to wait. And neither do the infants born with spinal muscular atrophy, a genetic mutation that often kills within twelve months of birth. He has already moved on to securing FDA approval for what would be the world's second clinical trial of human embryonic stem cells to test a different stem-cell-derived nerve cell — the motor neuron — on infants with SMA. This go-round, he wants to increase velocity. No dribbling out a paper here and there and waiting for his colleagues' comments. "This motor-neuron story, not a single publication out on it yet, but I'm going to the FDA!" trills Keirstead, forty-two. "I did everything at once this time: I did a manufacturing facility. I formulated the clinical plan, gathering all the medical doctors. I did the preclinical efficacy, preclinical safety, lined it all up side by side, moved it all forward." Sure, he has a handful of papers on his motor-neuron story in review, but those are almost an afterthought. Cures don't come from pushing paperwork.

Back in his office, where Keirstead awaits final word from the FDA on the oligodendrocytes trial, he points to a framed rejection letter. In regards to his pure nerve cells that most thought were an impossibility, a journal reviewer wrote: "If these findings are true, this would be the most meaningful discovery in the stem-cell field. But I simply don't believe it."

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