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Stem cells delay paralyzing disease

Stem cells delay paralyzing disease
Mon Oct 16, 2006 3:08 PM ET

By Maggie Fox, Health and Science Editor

WASHINGTON (Reuters) – Human fetal stem cells can graft onto the spines of rats and delay some of the paralyzing symptoms of motor neuron disease, commonly known as Lou Gehrig’s disease, U.S. researchers reported on Monday.

The new cells were resistant to the disease, also known as amyotrophic lateral sclerosis or ALS, the researchers said.

A company associated with the researchers is incubating batches of the human cells, taken from an aborted fetus, and hopes to market them as a treatment for several sorts of paralyzing conditions.

“We were extremely surprised to see that the grafted stem cells were not negatively affected by the degenerating cells around them, as many feared introducing healthy cells into a diseased environment would only kill them,” said Dr. Vassilis Koliatsos of Johns Hopkins University, who helped lead the study.

The researchers, who published their findings in the journal Transplantation, used specially bred rats that always develop symptoms of ALS and die. Like people with the disease, they gradually become paralyzed until they suffocate when breathing muscles stop working.

There is no cure for ALS and the causes are not clear. But the Johns Hopkins team wanted to see if grafting new cells into the body might help preserve some muscle function.

They used cells taken from an 8-week-old fetus, which had been donated by the mother after an abortion. Stem cells are partially developed but can give rise to a variety of different tissues if put into the right environment.

The cells from the aborted fetus are not the same as embryonic stem cells, currently at the center of a political debate in the United States. Fetal stem cells are intermediate between embryonic stem cells and so-called adult stem cells.

 
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They are somewhat more malleable than adult stem cells but not as plastic as embryonic stem cells.

In this case, the researchers took the cells from the developing spine. These cells are already destined to become nervous system tissue and do not elicit an immune rejection by the body, said Karl Johe, chairman and chief scientific officer of Neuralstem Inc. in Rockville, Maryland.

NO CURE

The researchers only transplanted cells into the lower spinal cords of the rats, in part because the animals are so tiny and the job is tricky, said Johe. Because the upper spinal cord controls the upper half of the body including breathing, there was no chance of curing the rats.

“They do develop symptoms and also they still die, but the onset is more slowly developing and the longevity is extended,” Johe said in a telephone interview.

They injected the human fetal stem cells into adult rats not yet showing symptoms and also killed some of the stem cells and injected them into other rats to act as a control.

On average, the rats treated with live stem cells started losing weight — one of the first symptoms of disease — after 59 days and they lived for 86 days. In contrast, the rats given the sham treatment started to lose weight at 52 days and only lived for 75 days.

While all the rats grew steadily weaker, the treated rats maintained their ability to crawl up a slope for much longer than untreated rats.

After the rats died the researchers examined their spines and saw that 70 percent of the transplanted cells had developed into nerve cells.

Johe said the company was growing and nurturing the cells and hoped to create many batches of purified cells that could be used for transplants for a range of patients with spinal cord diseases or injuries.

“If we see in a year … really significant effects (in rats) then I think we could be ready for a (human) clinical trial in another year after that,” Johe said

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Stem cells delay paralyzing disease

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Stem cells delay paralyzing disease
Mon Oct 16, 2006 3:08 PM ET

By Maggie Fox, Health and Science Editor

WASHINGTON (Reuters) – Human fetal stem cells can graft onto the spines of rats and delay some of the paralyzing symptoms of motor neuron disease, commonly known as Lou Gehrig’s disease, U.S. researchers reported on Monday.

The new cells were resistant to the disease, also known as amyotrophic lateral sclerosis or ALS, the researchers said.

A company associated with the researchers is incubating batches of the human cells, taken from an aborted fetus, and hopes to market them as a treatment for several sorts of paralyzing conditions.

“We were extremely surprised to see that the grafted stem cells were not negatively affected by the degenerating cells around them, as many feared introducing healthy cells into a diseased environment would only kill them,” said Dr. Vassilis Koliatsos of Johns Hopkins University, who helped lead the study.

The researchers, who published their findings in the journal Transplantation, used specially bred rats that always develop symptoms of ALS and die. Like people with the disease, they gradually become paralyzed until they suffocate when breathing muscles stop working.

There is no cure for ALS and the causes are not clear. But the Johns Hopkins team wanted to see if grafting new cells into the body might help preserve some muscle function.

They used cells taken from an 8-week-old fetus, which had been donated by the mother after an abortion. Stem cells are partially developed but can give rise to a variety of different tissues if put into the right environment.

The cells from the aborted fetus are not the same as embryonic stem cells, currently at the center of a political debate in the United States. Fetal stem cells are intermediate between embryonic stem cells and so-called adult stem cells.

 

They are somewhat more malleable than adult stem cells but not as plastic as embryonic stem cells.

In this case, the researchers took the cells from the developing spine. These cells are already destined to become nervous system tissue and do not elicit an immune rejection by the body, said Karl Johe, chairman and chief scientific officer of Neuralstem Inc. in Rockville, Maryland.

NO CURE

The researchers only transplanted cells into the lower spinal cords of the rats, in part because the animals are so tiny and the job is tricky, said Johe. Because the upper spinal cord controls the upper half of the body including breathing, there was no chance of curing the rats.

“They do develop symptoms and also they still die, but the onset is more slowly developing and the longevity is extended,” Johe said in a telephone interview.

They injected the human fetal stem cells into adult rats not yet showing symptoms and also killed some of the stem cells and injected them into other rats to act as a control.

On average, the rats treated with live stem cells started losing weight — one of the first symptoms of disease — after 59 days and they lived for 86 days. In contrast, the rats given the sham treatment started to lose weight at 52 days and only lived for 75 days.

While all the rats grew steadily weaker, the treated rats maintained their ability to crawl up a slope for much longer than untreated rats.

After the rats died the researchers examined their spines and saw that 70 percent of the transplanted cells had developed into nerve cells.

Johe said the company was growing and nurturing the cells and hoped to create many batches of purified cells that could be used for transplants for a range of patients with spinal cord diseases or injuries.

“If we see in a year … really significant effects (in rats) then I think we could be ready for a (human) clinical trial in another year after that,” Johe said.

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Human Stem Cells Help Rats to Fend Off Lou Gehrig’s Disease

Human Stem Cells Help Rats to Fend Off Lou Gehrig’s Disease

By Rob Waters

Oct. 15 (Bloomberg) — Neural stem cells transplanted into the spinal cords of rats from a human fetus slowed onset of a form of Lou Gehrig’s disease, a condition that attacks the nerve circuits that control movement.

Researchers placed the cells in rats genetically engineered to develop a form of the disease, also know as amyotrophic lateral sclerosis or ALS. The rodents with the cells were slower to show symptoms such as weight loss and diminished strength, and lived about 11 days longer over a 30-month life span.

The finding suggests stem cells can be grafted into damaged nervous systems for a clinical benefit, contradicting the belief of many scientists. It may also eventually offer hope to about 5,600 people in the U.S. who are diagnosed yearly with ALS, which is almost always fatal.

“The dogma was that the spinal cord can not make neurons, or allow engrafted cells to become neurons,” said Vassilis Koliatsos, the Johns Hopkins School of Medicine neurologist who led the study, in an Oct. 12 telephone interview. “The assumption was also that because this is a toxic environment where motor neurons are dying, the cells would die.”

These assumptions “are increasingly proven wrong” by this research and other recent studies, he said. Koliatsos’s study was published today in the journal Transplantation.

The transplanted cells, which developed into neurons, or nerve cells, formed connections to existing neurons that had been damaged by the disease and were able to convey information through electrical signals and deliver proteins to help nourish the sick cells, Koliatsos said.

Neuralstem Inc.

The researchers used a line of neural stem cells developed by Neuralstem Inc., a closely held biotechnology company based in Rockville, Maryland. The company developed the line from fetal tissue donated by a woman who underwent an elective abortion at 8 weeks.

The stem cells, taken from an area near the developing spinal cord of the fetus, have the theoretical ability to develop or differentiate into any of three cell types found in the nervous system. The cells were kept alive in culture and chemically manipulated to keep them from differentiating.

The researchers exposed the spinal cords of the rats and used a tiny micropipette to inject cells. Rats in one group were given about 400,000 living neural stem cells; another control group was injected with dead cells.

The rats that got the live cells began losing weight at about 59 days on average, a week later than the rats in the control group. When made to walk an uphill plank as a strength test, the cell-treated rats performed better over a longer period of time. They also lived to about 86 days, 11 days longer than the control rats.

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When the rats were examined after their deaths, the researchers found that more than 70 percent of the transplanted stem cells had developed into nerve cells, and that many grew endings that connected to other cells, allowing them to transfer nerve impulses that direct muscular action and movement.

“These cells became neurons and they also made connections to sick neurons,” he said. “If you make connections to sick neurons, you close the circuit, you give them information.”

The connections allowed needed proteins and growth factors produced by the new neurons to pass to the damaged cells. This may help solve a problem that has vexed researchers. When scientists have delivered these proteins and growth factors, also known as trophic factors, using drugs, they reached unwanted targets and caused side effects, Koliatsos said.

`Delivers the Goods’

“You use the stem cell as a very complex biological structure or machine that manufactures and sends these trophic factors where they ought to be given,” he said. “It delivers the goods right on target.”

In this experiment, stem cells were injected in the portion of the spinal cord that controls the lower body. The next step, which Koliatsos has already begun working on, is to deliver the cells to the part of the spinal cord that controls upper body motion, including chest wall expansion and breathing.

“We need to do that, see if it’s well tolerated and see if we can extend their survival longer,” Koliatsos said. After that, he said, he’ll start thinking about how to study this type of treatment in people.

About 30,000 Americans have Lou Gehrig’s disease, according to the ALS Association. The disease begins with weakness in the arms and legs, and progresses to paralysis as motor neurons are damaged.

The study was funded by the National Institutes of Health, the Muscular Dystrophy Association and the university’s Robert Packard Center for ALS Research.

To contact the reporter on this story: Rob Waters in San Francisco at rwaters5@bloomberg.net .

Last Updated: October 15, 2006 00:58 EDT