UW scientists slow ALS using stem cells

UW scientists slow ALS using stem cells
Todd Finkelmeyer — 9/16/2008 11:53 am
Using engineered adult stem cells from bone marrow to deliver a growth factor directly to atrophied muscles, scientists at UW-Madison have successfully slowed the progression of amyotrophic lateral sclerosis (ALS) -- also known as Lou Gehrig's disease -- in rats.
The finding was published Tuesday in the journal Molecular Therapy.
Although it's at a relatively early stage, the research offers hope that the process might someday provide a new therapy for people who suffer from the debilitating and fatal disease, which is caused by the progressive loss of motor neurons and their connections to muscles.
There currently are no effective treatments for ALS.
"I don't want to give patients too much expectations," said Masatoshi Suzuki, the UW-Madison associate scientist who led the study out of the Waisman Center . "But so far the application is showing a lot of promise."
The study builds on previous research that showed motor neurons, the key cells that connect muscles to the central nervous system, could be protected by stem cells that carried a key growth component, glial cell line-derived neurotrophic factor (GDNF).
Past work by Suzuki and Clive Svendsen, a UW-Madison professor of neurology, showed that transplanting neural stem cells into the spinal cord could protect motor neurons that degenerate in an ALS rat model. But the motor neurons still didn't effectively connect with the muscles that atrophy due to ALS.
In the new study, Suzuki and his colleagues used adult bone marrow stem cells that were engineered to release GDNF directly to the muscle as sort of "Trojan horses" to deliver a growth factor. In the past, it was shown that bone marrow stem cells on their own had a modest effect, possibly by releasing their own protective factory.
But in the new research, the scientists delayed the progression of the disease and extended the lifespan of the afflicted animals. The Wisconsin group reported that the engineered cells survive well when introduced to muscle and significantly increased the number of neuromuscular connections and motor neurons in the spinal cord at mid stages of the disease.
"The positive effects that we reported in the paper are not so big," said Suzuki. "But they are important. So now we are working on modifying our method and enhancing the positive effects."
Although the study could someday lead to treatments for the disease, Suzuki cautioned that work remains before it could be attempted in humans.
Co-authors of the new Molecular Therapy report include Jacalyn McHugh, Craig Tork, Brandon Shelley and Antonio Hayes, all of UW-Madison; Ilaria Bellantuono of the Royal Manchester Children's Hospital, United Kingdom; and Patrick Aebischer of the Ecole Polytechnique Fdrale de Lausanne, Switzerland.
The new study was supported by grants from the ALS Association, the National Institutes of Health, the University of Wisconsin Foundation and the Les Turner ALS Foundation.

http://www.madison. com/tct/mad/ breaking_ news/305115

Using engineered adult w ALS using stem cells
Todd Finkelmeyer — 9/16/2008 11:53 am stem cells from bone marrow to deliver a growth factor directly to atrophied muscles, scientists at UW-Madison have successfully slowed the progression of amyotrophic lateral sclerosis (ALS) -- also known as Lou Gehrig's disease -- in rats.
The finding was published Tuesday in the journal Molecular Therapy.
Although it's at a relatively early stage, the research offers hope that the process might someday provide a new therapy for people who suffer from the debilitating and fatal disease, which is caused by the progressive loss of motor neurons and their connections to muscles.
There currently are no effective treatments for ALS.
"I don't want to give patients too much expectations," said Masatoshi Suzuki, the UW-Madison associate scientist who led the study out of the Waisman Center . "But so far the application is showing a lot of promise."
The study builds on previous research that showed motor neurons, the key cells that connect muscles to the central nervous system, could be protected by stem cells that carried a key growth component, glial cell line-derived neurotrophic factor (GDNF).
Past work by Suzuki and Clive Svendsen, a UW-Madison professor of neurology, showed that transplanting neural stem cells into the spinal cord could protect motor neurons that degenerate in an ALS rat model. But the motor neurons still didn't effectively connect with the muscles that atrophy due to ALS.
In the new study, Suzuki and his colleagues used adult bone marrow stem cells that were engineered to release GDNF directly to the muscle as sort of "Trojan horses" to deliver a growth factor. In the past, it was shown that bone marrow stem cells on their own had a modest effect, possibly by releasing their own protective factory.
But in the new research, the scientists delayed the progression of the disease and extended the lifespan of the afflicted animals. The Wisconsin group reported that the engineered cells survive well when introduced to muscle and significantly increased the number of neuromuscular connections and motor neurons in the spinal cord at mid stages of the disease.
"The positive effects that we reported in the paper are not so big," said Suzuki. "But they are important. So now we are working on modifying our method and enhancing the positive effects."
Although the study could someday lead to treatments for the disease, Suzuki cautioned that work remains before it could be attempted in humans.
Co-authors of the new Molecular Therapy report include Jacalyn McHugh, Craig Tork, Brandon Shelley and Antonio Hayes, all of UW-Madison; Ilaria Bellantuono of the Royal Manchester Children's Hospital, United Kingdom; and Patrick Aebischer of the Ecole Polytechnique Fdrale de Lausanne, Switzerland.
The new study was supported by grants from the ALS Association, the National Institutes of Health, the University of Wisconsin Foundation and the Les Turner ALS Foundation.

http://www.madison. com/tct/mad/ breaking_ news/305115