Navigation Links
Engineered Stem Cells Show Promise For Sneaking Drugs Into The Brain

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 fu nction 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.


'"/>

Source:University of Wisconsin-Madison


Related biology news :

1. Engineered molecule amplifies bodys immune response
2. Engineered skin offers clues to melanoma development
3. Engineered mouse mimics cognitive aspects of schizophrenia
4. Engineered heart tissue offers insights into irregular heartbeats, defibrillator failure
5. Engineered yeast speeds ethanol production
6. Jump-starting T Cells In Skin Cancer
7. Emory Study Tests Bone Marrow Stem Cells to Improve Circulation in Legs
8. Transplantation Of Monkey Embryonic Stem Cells Reverses Parkinson Disease In Primates
9. Fundamental Finding Yields Insight into Stem Cells, Cancer; Opens Door to Drug Discovery
10. Weill Cornell Research Reveals Secrets Of Trafficking Within Cells
11. First-ever Compounds To Target Only Metastatic Cells Are Highly Effective Against Breast, Prostate, And Colon Cancers
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/9/2016)... TURKU, Finland , June 9, 2016 ... French National Police deploy Teleste,s video security solution to ensure ... France during the major tournament ... and data communications systems and services, announced today that its ... Police Prefecture to back up public safety across ...
(Date:6/2/2016)... Perimeter Surveillance & Detection Systems, ... Infrastructure, Support & Other Service  The latest ... comprehensive analysis of the global Border Security market ... of $17.98 billion in 2016. Now: In ... in software and hardware technologies for advanced video surveillance. ...
(Date:5/12/2016)... -- WearablesResearch.com , a brand of Troubadour Research ... the Q1 wave of its quarterly wearables survey. A ... to a program where they would receive discounts for ... "We were surprised to see that so ... , CEO of Troubadour Research, "primarily because there are ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... 2016 , ... Cancer experts from Austria, Hungary, Switzerland, and ... new and helpful biomarker for malignant pleural mesothelioma. Surviving Mesothelioma has just published ... , Biomarkers are components in the blood, tissue or body fluids that ...
(Date:6/27/2016)... ... 2016 , ... Newly created 4Sight Medical Solutions ... healthcare market. The company's primary focus is on new product introductions, to include ... are necessary to help companies efficiently bring their products to market. , The ...
(Date:6/27/2016)... 2016  Liquid Biotech USA ... a Sponsored Research Agreement with The University of ... from cancer patients.  The funding will be used ... with clinical outcomes in cancer patients undergoing a ... be employed to support the design of a ...
(Date:6/24/2016)...  Regular discussions on a range of subjects including policies, ... entities said Poloz. Speaking at a lecture to ... he pointed to the country,s inflation target, which is set ... "In certain areas there needs ... economic goals, why not sit down and address strategy together?" ...
Breaking Biology Technology: