Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The neighborhood matters: Packard Center scientists show cell environment is important in ALS

06.10.2003


In amyotrophic lateral sclerosis (ALS), neighborhood may be everything, if a new study in mouse models of the disease holds true for patients.



ALS, or Lou Gehrig’s disease, brings about a gradual death of the motor neurons that activate muscles. Paralysis follows. But according to work described today in the journal Science, the cells that are next to motor neurons -- but aren’t themselves nerve cells -- can play a major role in advancing or limiting the disease.

"What we’ve been given is a new principle for extending survival or, perhaps, overcoming ALS, based on how many healthy cells surround an ailing motor nerve cell," says Don Cleveland, Ph.D., a scientist with The Packard Center for ALS Research at Johns Hopkins and, with Larry Goldstein, Ph.D., co-leader of the research team. "All this has great implications for stem cell therapy," he adds. "We now believe delivery of normal, non-neuronal cells to spinal cords could be completely protective, even without replacement of a single motor neuron."


In a series of experiments, the team measured the effect of having different proportions of healthy cells to at-risk cells in mice, clocking their survival time. Normally, the scientists work with standard animal models of ALS. Those mice or rats carry a mutant human gene -- called SOD1 -- that triggers a rare, inherited form of the disease in people. In these models, every cell carries a mutant SOD1 gene. The animals typically slip into death by the time they’re six to eight months of age.

But in this study, the researchers used chimeric animals -- mice engineered to be a mix of normal cells, also called wild type, and cells containing the mutant SOD1 gene. They tagged the cells with molecular flags to make it clear which were which. The percent of wild-type cells in the animals’ spinal cords ranged from 5 to 90 percent.

Having wild type cells mixed in had the effect of extending mouse survival from one to eight months, depending on the number of cells and type of SOD1 mutation. In a second group of chimeric mice, brought about by a different technique and with a different type of tracer, the animals survived disease-free until sacrificed for study at an age at least twice the age at which typical SOD1 animal models die.

Even though further study showed that as high as three-fourths of the motor neurons in the animals’ spinal cords carried the mutant gene, all the motor neurons remained amazingly healthy, apparently from having healthy non-neuronal cells in the neighborhood. This was especially true of the second batch of mice, which had no microscopic evidence of disease.

"It’s really striking," says Cleveland, "to see what a small number of normal cells effectively eliminated damage to motor neurons from the ALS-causing genetic error."

The opposite effect also appeared: mice with normal motor neurons but with surrounding cells carrying an SOD1 mutation showed early signs of disease. Normal neurons, then, can apparently acquire something toxic from at-risk non-neuronal neighboring cells.

"So we’re seeing a real-life metaphor here," says Cleveland. "Living in a bad environment can damage good cells. And more important, restoring a better environment to ’bad’ neurons by surrounding them with healthy neighbors can significantly lessen toxic effects. In some cases, having normal cells completely stops motor neuron death."

Research conducted by Center scientist and team member Jean-Pierre Julien, Ph.D., at Laval University in Quebec was a key contribution to the results. Researchers Cleveland and Goldstein are both at the University of California, San Diego, where Cleveland heads the Laboratory of Cell Biology at the Ludwig Institute for Cancer Research.

The research was funded by the Packard Center for ALS Research at Johns Hopkins, Project ALS, The ALS Association, the U.S. National Institutes of Health, the Canadian Institutes of Health Research, The Angel Fund for ALS Research and the U.S. Veterans Administration.

Headquartered in Baltimore, the Robert Packard Center for ALS Research at Johns Hopkins is a collaboration of scientists worldwide who are working aggressively to develop new treatments and a cure for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. The Center is the only institution of its kind dedicated solely to the disease. Its research is meant to translate from the laboratory bench to the clinic in record time.

Joanna Downer | EurekAlert!
Further information:
http://www.hopkinsmedicine.org/

More articles from Health and Medicine:

nachricht UIC researchers find unique organ-specific signature profiles for blood vessel cells
18.02.2020 | University of Illinois at Chicago

nachricht Remdesivir prevents MERS coronavirus disease in monkeys
14.02.2020 | NIH/National Institute of Allergy and Infectious Diseases

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

Im Focus: Skyrmions like it hot: Spin structures are controllable even at high temperatures

Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices

The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...

Im Focus: Making the internet more energy efficient through systemic optimization

Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.

Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.

Im Focus: New synthesis methods enhance 3D chemical space for drug discovery

After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.

"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.

Im Focus: Quantum fluctuations sustain the record superconductor

Superconductivity approaching room temperature may be possible in hydrogen-rich compounds at much lower pressures than previously expected

Reaching room-temperature superconductivity is one of the biggest dreams in physics. Its discovery would bring a technological revolution by providing...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

Movement of a liquid droplet generates over 5 volts of electricity

18.02.2020 | Power and Electrical Engineering

Powering the future: Smallest all-digital circuit opens doors to 5 nm next-gen semiconductor

18.02.2020 | Information Technology

Studying electrons, bridging two realms of physics: connecting solids and soft matter

18.02.2020 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>