Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New UW study offers strategy for treatment of fatal nervous system disorder

13.12.2005


Working with mice, University of Wisconsin-Madison researchers have developed the basis for a therapeutic strategy that could provide hope for children afflicted with Krabbe’s disease, a fatal nervous system disorder.

Writing this week (Dec. 12, 2005) in the Proceedings of the National Academy of Sciences (PNAS), a team of researchers at the UW-Madison School of Veterinary Medicine describes experiments that effectively promoted the ability of defective cells to take up and utilize an enzyme that is essential for the maintenance of a critical sheathing of nerve fibers.

The work centers on devising strategies to treat inherited diseases of the nervous system in which cells fail to maintain myelin, a protective sheathing that envelops nerve fibers and acts like the insulation on an electric wire. Myelin ensures the effective transmission of the signals routinely conducted by the nervous system. For those afflicted with Krabbe’s disease, the loss of myelin results in arrested motor and mental development, seizures, paralysis and, ultimately, death.



The Wisconsin experiments, led by Ian Duncan, a UW-Madison professor of medical sciences who is an expert on diseases of myelin, explored how cells obtained from a mouse model of Krabbe’s disease could be reinvigorated by replacing a missing enzyme, and thus allow the healthy maintenance of myelin.

In the case of Krabbe’s disease, myelination begins normally in early development. But the absence in myelin-forming cells of a key enzyme known as galactocerebrosidase leads to the death of the cells and, subsequently, the loss of myelin. "Our hypothesis was that if you provided the (flawed) myelinating cells with the enzyme, the cells would maintain the myelin as healthy cells would," says Duncan, the senior author of the PNAS paper who planned and conducted the experiments with lead author Yoichi Kondo, a postdoctoral fellow working in Duncan’s lab.

Simply supplying the enzyme directly to the brain and spinal cord is complicated by a natural barrier -- the blood-brain barrier -- that makes the delivery of agents like the enzyme to the brain difficult.

"To eliminate the barrier, we changed the paradigm by transplanting enzyme-deficient cells into the brain and spinal cord of another type of mouse which can provide the enzyme," explains Duncan.

The Wisconsin group isolated progenitor cells from the mouse model of Krabbe’s disease. Transplanting the cells to the brain and spinal cord of another type of mouse that lacks any myelin, the group observed that the implanted cells took up the enzyme from the host cells and sparked widespread and persistent myelination of the brain and spinal cord.

"The donor cells are stable and survive and, biochemically, enzyme levels in the graft were restored to normal," says Kondo.

Enzyme replacement therapy, Duncan notes, is not a new idea for treating such inherited demyelinating diseases. For example, work by other groups involving transplants of bone marrow and umbilical cord blood in Krabbe’s patients have been attempted with some success.

But no one knew if the missing enzyme could be replaced in key cells known as oligodendrocytes, thus allowing maintenance of stable myelin throughout the nervous system.

"This experimental strategy proves that oligodendrocytes can survive and maintain myelin when transplanted into an environment where the missing enzyme is available," says Kondo.

Krabbe’s disease is perhaps best known to the public through the efforts of Hall of Fame quarterback Jim Kelly, whose late son Hunter was afflicted with the disease and who established a foundation, Hunter’s Hope, to promote awareness and research. The new study was funded by Hunter’s Hope.

Krabbe’s disease is one of a number of diseases caused by the inability to produce and maintain myelin. It afflicts about 1 in every 100,000 people and treatment options are limited at best.

The new work, the authors emphasize, provides proof of principle for a new therapeutic strategy, but any therapy developed on the group’s new insights will require further study.

Ian Duncan | EurekAlert!
Further information:
http://www.vetmed.wisc.edu

More articles from Studies and Analyses:

nachricht Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland

nachricht Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>