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Paralyzed Rats Walk in Stem Cell Study

Paralyzed rats walk in stem cell study

Hopkins scientists say their method shows potential to help people suffering from neurological disorders

By Chris Emery
Sun reporter

A team of Johns Hopkins researchers has restored movement to paralyzed rats using a new method that they say shows the potential of embryonic stem cells to restore function to humans suffering from neurological disorders.

"For the first time we have used stem cells to rewire part of the nervous system," said Dr. Douglas Kerr, the lead researcher.

The multipronged procedure, which requires the use of drugs and proteins as well as implanted stem cells, re-established the electrical path from the rats' brains, down their spinal cords and out to their muscles, Kerr said.

The results, released yesterday, are to be published in the journal Annals of Neurology. The study was funded by several organizations, including the National Institutes of Health and the Muscular Dystrophy Association,

One obstacle to applying the treatment to people is the length of the spinal cord, said Clive N. Svendsen, a researcher at the University of Wisconsin. He said implanted stem cells would have to grow farther to reach inactive muscles and that it is difficult to get spinal neurons to survive when transplanted into humans.

"It is a great proof-of-concept paper, but it doesn't address everything," Svendsen said of the Hopkins study.

Kerr said he is planning a study in pigs to determine whether his team's technique will work in larger mammals.

Clinical trials in humans are a possibility within five years, said Kerr, but he cautioned that human therapy is years away.

Yet, he says the work is a big step forward in the quest for a cure for paralysis and other neurological disorders.

"It's not imminent, but it is a realistic hope," he said. "It used to be science fiction, but it is now a realistic possibility."

He said the speed at which his research progresses would in large part be dictated by the availability of funding, which has become more difficult to obtain in the face of political opposition to research on human embryos.

In their Baltimore laboratory, Kerr and his colleagues inserted mouse stem cells into the spinal cords of paralyzed rats that had little or no use of their hind limbs. Kerr and his team initially paralyzed the rats with a virus that killed the neurons that connected their spinal cords to their leg muscles.

The scientists then used a cocktail of proteins and drugs to coax the implanted nerve cells to make connections with spinal nerves coming from the brain and to grow out of the spinal cord to connect with the animals leg muscles.

Of the 15 rats that received the full treatment in the study, 11 showed significant improvement in their ability to control their hind limbs 24 weeks after the stem cells were implanted.

The scientists found that if any one of the factors was removed from the treatment - the stem cells or any of the two proteins and three drugs they used - the rats showed no improvement in their ability to stand and walk. The most important finding, Kerr said, was that all of the factors were needed for the animals to regain function.

"This is a blueprint for how to rewire part of the nervous system," he said.

He said the results suggest that embryonic stem cells may one day be used to treat human neurological disorders such as Lou Gehrig's disease, multiple sclerosis and spinal injuries.

The researchers used embryonic stem cells because they possess the unique ability to become any other type of cell.

Before the cells were implanted, the researchers stimulated them with a cellular protein and Retin-A, an organic compound that plays a role in the growth and development of embryos. That prompted some of the stem cells to begin developing into nerve cells.

The researchers then implanted tens of thousands of the cells into the rats' spinal cords. Next, the team injected another protein near the rats' leg muscles to coax the cells to grow out of the spinal cord and attach to the muscles.

"This is very different than a lot of what's been reported on in recent years," said Naomi Kleitman, a neurology researcher at the National Institute of Neurological Disorders and Stroke. "I haven't seen anything like it before."

She said most studies have focused on the nerve cells in the spinal cord that connect to the brain. Kerr's protocol focuses on cells known as lower motor neurons, which connect the spinal cord to muscles.

"If I want to move my arm or my leg, my brain has to tell my spinal cord and my spinal cord has to tell my muscles," she said. "This research looks at fixing the problem of what happens when nobody is there to answer that call."

Despite the success of the study, Kerr expressed concern that he might struggle to obtain funding if he tries to extend his research to humans.

"The amount of money required to take this into clinical trials is ultimately hundreds of millions of dollars," he said. "Without federal funding, that money is going to be difficult to find."

Early last year, President Bush restricted federal funding of embryonic stem cell research. Bush and some other religious conservatives oppose research using embryonic stem cells, citing ethical concerns.

But Kerr said his team had to use embryonic stem cells because adult stem cells could not be coaxed into developing into spinal neurons and healthy adult neurons die when implanted into the spinal cord.

To make up for the loss of federal money, several states - including Maryland - have begun offering state funding to embryonic stem cell researchers.

This spring, the General Assembly voted to provide $15 million in state funding to stem cell researchers in Maryland.

Kerr said he plans to apply for state funding once the commission that is to administer the research grants has been formed.

Source Newsday.com