Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Engineered stem cells show promise for sneaking drugs into the brain

15.12.2005


One of the great challenges for treating Parkinson’s diseases and other neurodegenerative disorders is getting medicine to the right place in the brain.



The brain is a complex organ with many different types of cells and structures, and it is fortified with a protective barrier erected by blood vessels and glial cells -- the brain’s structural building blocks -- that effectively blocks the delivery of most drugs from the bloodstream.

But now scientists have found a new way to sneak drugs past the blood-brain barrier by engineering and implanting progenitor brain cells derived from stem cells to produce and deliver a critical growth factor that has already shown clinical promise for treating Parkinson’s disease.


Writing this week (Dec. 15, 2005) in the journal Gene Therapy, University of Wisconsin-Madison neuroscientist Clive Svendsen and his colleagues describe experiments that demonstrate that engineered human brain progenitor cells, transplanted into the brains of rats and monkeys, can effectively integrate into the brain and deliver medicine where it is needed.

The Wisconsin team obtained and grew large numbers of progenitor cells from human fetal brain tissue. They then engineered the cells to produce a growth factor known as glial cell line-derived neurotrophic factor (GDNF). In some small but promising clinical trials, GDNF showed a marked ability to provide relief from the debilitating symptoms of Parkinson’s. But the drug, which is expensive and hard to obtain, had to be pumped directly into the brains of Parkinson’s patients for it to work, as it is unable to cross the blood-brain barrier.

In an effort to develop a less invasive strategy to effectively deliver the drug to the brain, Svendsen’s team implanted the GDNF secreting cells into the brains of rats and elderly primates. The cells migrated within critical areas of the brain and produced the growth factor in quantities sufficient for improving the survival and function of the defective cells at the root of Parkinson’s.

"This work shows that stem cells can be used as drug delivery vehicles in the brain," says Svendsen, a professor of anatomy whose laboratory is at the UW-Madison Waisman Center.

The new Wisconsin study, whose lead author is Soshana Behrstock, depended on formative brain cells that were coaxed from blank-slate stem cells. The progenitor neural cells were genetically modified to secrete the growth factor when implanted in the striatum, a large cluster of cells in the brain that controls movement, balance and walking.

To work effectively, the cells in the striatum require dopamine, a chemical that is produced deep in the brain and that travels up nerve fibers to the striatum where it is used to keep critical cells functional. Loss of the ability to produce dopamine is the root cause of Parkinson’s, a disease that afflicts about 1.5 million people in the United States.

In the new Wisconsin study, the GDNF-producing cells transplanted in the striatum of animals with a condition like Parkinson’s showed not only that a critical drug could be delivered to the right place, but that the drug was delivered in a way that promoted its therapeutic potential. The researchers reported new nerve fiber growth in the striatum and the transport of the critical nerve growth factor GDNF from the striatum to the substantia niagra, the part of the brain that harbors the cells that produce dopamine.

"In Parkinson’s, the striatum loses fibers," Svendsen explains. But cells in the striatum exposed to GDNF in the Wisconsin study showed an ability to recover and sprout new fibers.

"It actually seems to work better in the terminal (striatum)," Svendsen says. "The bonus is it gets transported back to the substantia niagra."

The transplanted cells, according to Behrstock, survived and continued to produce GDNF in laboratory animals for up to three months.

One hurdle that needs to be overcome before such a technique could be attempted in human patients, says Svendsen, is developing a method to switch transplanted cells on or off and thus control their drug delivery capabilities. Working with engineered cells in culture, the Wisconsin group found they could switch the cells on and off using a second drug. Doing so in animal models, however, was more difficult and the issue will need to be addressed in new experiments, according to Svendsen.

The new study, Svendsen argues, proves that progenitor cells -- cells that can now be made in large quantities in the laboratory -- can be crafted to help clinicians deliver drugs where they are needed most in the body. Delivering medicine to the brain, whose blood-brain barrier effectively excludes more than 70 percent of all drugs, would be an especially valuable use for the cells. Such a new method may be useful for treating a number of neurodegenerative diseases beyond Parkinson’s, he says.

In addition to Svendsen and Behrstock, authors of the new Gene Therapy paper include Allison Ebert, Jacqueline McHugh, Stephen Vosberg, Elizabeth Capowski, Bernard Schneider and Derek Hei, all of UW-Madison; Jeffery Kordower of Rush University Medical Center; and Patrick Aebischer of the Swiss Federal Institute of Technology.

Clive Svendsen | EurekAlert!
Further information:
http://www.wisc.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

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

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>