SCIENTISTS REPORT PROGRESS TOWARD STEM CELL THERAPY FOR ALS

SAN DIEGO, Nov. 14, 2001 — In recent months, scientists have been forging ahead with plans to develop a stem cell-based treatment for amyotrophic lateral sclerosis (ALS) — a rapidly paralyzing, fatal disease caused by the death of muscle-controlling nerve cells (motor neurons) in the spinal cord.

At an ALS-focused press conference Monday during the annual Society for Neuroscience meeting in San Diego, researchers announced progress on several fronts.

Stem cells — immature cells that generate all our cells during early life and persist in small numbers during adulthood — are being hailed as a possible "fix-all" for degenerative diseases like ALS. Many scientists hope to treat ALS by using transplants of healthy neural stem cells to repair or replace damaged motor neurons.

Last year, a research team led by Jeffrey Rothstein at Johns Hopkins University in Baltimore moved toward that goal by testing stem cells on rodents with an ALS-like disease caused by a virus. When the group injected the cells into the paralyzed rodents' spinal cords, the rodents regained some movement in their hindlegs.

But those experiments were just the tip of the iceberg in the process required for bringing stem cells into clinical trials in ALS, says Rothstein, who co-directs the Muscular Dystrophy Association’s ALS center at Johns Hopkins.

Safety Concerns

Before stem cells can be tested in people with ALS, researchers first need to know whether stem cell transplants are safe, Rothstein said. There's concern that because stem cells can multiply and create new cells, they might form tumors.

Rothstein's team, along with a group led by Ted Teng at Harvard Medical School in Boston, have now begun to test stem cell therapy in an animal that's closely related to humans — the monkey.

First, they gave monkeys an ALS-like condition by injecting a plant-derived toxin called ricin into nerves in the monkeys' legs. The ricin killed motor neurons in the part of the spinal cord connected to those nerves, causing paralysis of the injected leg. Then, they injected stem cells into the fluid-filled space within the spinal cord.

"Six months after stem cell delivery, there's no obvious adverse effect," Rothstein said. "The cells don't do anything toxic to the spinal cord."

Some of the stem cells appeared to incorporate into the spinal cord, and none appeared in other tissues far away from the site of delivery — a good sign that the cells won't disperse and form tumors.

"But what everyone really wants to know is: Did the cells do any good?" Rothstein admitted. "We do know there's some improvement in the physiological properties of the limb, but that's really not enough to hang our hat on yet."

The Magic Bullet?

Before moving to the clinic, Rothstein and other ALS researchers are also trying to figure out which stem cells pack the most punch for repairing damage to the spinal cord.

Rothstein and Teng have tested different kinds of stem cells — from mice and humans, from different tissues and different stages of development -– with various results.

In Teng's experiments on monkeys, one class of stem cells — human neural stem cells — appeared to become neurons and make connections with other neurons in the spinal cord.

Another group, led by Alison Willing at the University of South Florida in Tampa, has been investigating human NT neurons — a laboratory-grown line of cells that aren't really stem cells, but can divide to produce neurons.

Willing's group transplanted those cells into mice that have a mutant gene underlying familial ALS, and found "striking results," Willing said. When treated early in the disease, the mice developed ALS one month later and lived two weeks longer than untreated mice. When given to mice in advanced stages of ALS, the transplants didn't affect survival but slowed progression of the disease.

Whichever stem cells turn out to be ideal for regenerating motor neurons lost to ALS, Rothstein said stem cells alone are unlikely to provide a cure.

"People in the ALS field don't think about individual therapies as the answer to ALS. We have to focus on therapies one at a time right now, but we know we'll probably have to use them in combination to effectively treat ALS," he explained.

Clinical trials are under way for several drugs that might work against ALS, including the arthritis drug Celebrex and the breast cancer drug tamoxifen.