October 9, 2009

Packard Scientist to Run First Human Stem Cell Trial for ALS

Before long, Packard Center investigator Jonathan Glass should be conducting the first FDA-approved trial of stem cells for ALS. The Phase I trial - which aims to test safety of both the cells and the procedure for implanting them - involves injecting human neural stem cells into patients' spinal cords.

Later trials, if the surgical procedure and cell injections are safe, could be carried out to show if the cells are effective in spinal cord repair or regeneration. It’s important to know that this first trial is not designed to determine if the cells will alter disease progression:  Phase 1 trials are designed only to be sure the procedures and therapies are possible and safe in humans.

The study site is solely at Emory University where Glass directs their neuromuscular laboratory. He's also Director of the Emory ALS Center and a world-respected scientist in that disease. Eva Feldman, who directs the University of Michigan ALS Clinic, is the project's overall leader.

In this first stage, 12 patients will receive from five to ten stem cell injections to the lumbar spinal cord. The final review comes two years later.

A Maryland-based biotech company, Neuralstem, both launched the research and will provide the human neural stem cells that it uses. Unlike, say, embryonic stem cells, which have the capacity to become any cell type, neural stem cells have been nudged a little farther down the developmental line. The cells appear identical to the semi-specialized stem cells in humans that go on to become nerve cells.

The original "proof of principle" work - the study that showed this particular type of neural stem cell might repair the spinal cord, came from Packard-funded research in 2005. Packard scientist Vassilis Koliatsos at Johns Hopkins first showed the stem cells could survive well in culture and that they could safely be injected into rat models of ALS (the SOD1 G93A rat). Also, he showed that they could remain stable in the spinal cord and could morph into neurons.

Most important, the earlier Packard research revealed that the newly created neurons integrated themselves into natural spinal cord motor neuron circuits. The grafts - injected only into the lumbar spinal cord and not the entire diseased organ - delayed the onset of ALS in the rats and extended their life span almost two weeks.

Later work elsewhere showed the cells could reverse paralysis in rats with ischemic spastic paraplegia, a more rapid, localized spinal cord damage. Still, the scientific community realizes that the ability of these models to predict response in human disease has not yet been firmly established.

As for the present trial, although the FDA approved it this September, no date has yet been set for its start at Emory. That's because it's awaiting approval by that university's institutional review board, a process, the Emory web site states, "could take weeks or months."

Glass has been with the Packard Center since its early days almost a decade ago. Since its inception, the Center has supported solid, creative stem cell research. "The development of cellular therapy is exciting," says Jeffrey Rothstein, Packard director. "The lessons we have collectively learned over the last 10 years from animal research tell us that the human trials must be very carefully designed and executed - even the novel surgical approaches by which the cells are delivered.

"We all hope that this first clinical trial will provide insight in how to carry out cellular therapy."

Meanwhile, research with another stem cell type, those that give rise to the key spinal cord cells, astrocytes, is moving closer to human trials under Center investigator, Nicholas Maragakis, in conjunction with Q Therapeutics, a Utah biotech firm.

"We’re not all about stem cells, however," adds Rothstein. "The Packard Center's translational program focuses on the early development of a variety of approaches to ALS treatment that includes novel drugs, gene inactivation, and cellular therapy."