Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Reprogramming Brain Cells Important First Step for New Parkinson's Therapy, Penn Study Finds

14.12.2011
Researchers convert astrocytes directly into dopamine-producing nerve cells of the midbrain

In efforts to find new treatments for Parkinson’s Disease (PD), researchers from the Perelman School of Medicine at the University of Pennsylvania have directly reprogrammed astrocytes, the most plentiful cell type in the central nervous system, into dopamine-producing neurons. PD is marked by the degeneration of dopaminergic neurons in the midbrain. Dopamine is a brain chemical important in behavior and cognition, voluntary movement, sleep, mood, attention, and memory and learning.


Dopaminergic neurons generated by directly reprogramming astrocytes. Green stain denotes expression of tyrosine hydroxylase, an enzyme required for dopamine synthesis.
Credit: Russell Addis, PhD, Perelman School of Medicine, University of Pennsylvania

“These cells are potentially useful in cell-replacement therapies for Parkinson’s or in modeling the disease in the lab,” says senior author John Gearhart, PhD, director of the Institute for Regenerative Medicine (IRM) at Penn. The team reports their findings in PLoS One.

“Our study is the first to demonstrate conversion of astrocytes to midbrain dopaminergic neurons, opening the door for novel reprogramming strategies to treat Parkinson’s disease,” says first author Russell C. Addis, PhD, a senior research investigator with IRM.

A Different Approach
Parkinson’s affects different areas of the brain but primarily attacks the dopamine-producing section called the substantial nigra. Cells in this region send dopamine to another region called the striatum, where it is used to regulate movement. The chemical or genetic triggers that kill dopamine neurons over time is at the heart of understanding the progressive loss of these specialized cells.

As many as one million people in the US live with PD, according to the Parkinson’s Disease Foundation. Symptoms include tremors, slowness of movements, limb stiffness, and difficulties with gait and balance.

Limited success in clinical trials over the last 15 years in transplanting fetal stem cells into the brains of Parkinson’s disease patients has spurred researchers to look for new treatments. Using PET scans, investigators have been able to see that transplanted neurons grow and make connections, reducing symptoms for a time. Ethical issues about the source of embryonic stem cells; the interaction of cells with host cells; the efficiency of stems cells to reproduce, and their long-term viability and stability are all still concerns about trials using dopaminergic cell transplants to treat Parkinson’s.

First Steps
In the first step towards a direct cell replacement therapy for Parkinson’s, the team reprogrammed astrocytes to dopaminergic neurons using three transcription factors – ASCL1, LMX1B, and NURR1 – delivered with a lentiviral vector.

The process is efficient, with about 18 percent of cells expressing markers of dopaminergic neurons after two weeks. The next closest conversion efficiency is approximately 9 percent, which was reported in another study.

The dopamine-producing neurons derived from astrocytes showed gene expression patterns and electrophysiolgical properties of midbrain dopaminergic neurons, and released dopamine when their cell membranes were depolarized.

The Penn team is now working to see if the same reprogramming process that converts astrocytes to dopamine-producing neurons in a dish can also work within a living brain – experiments will soon be underway using gene therapy vectors to deliver the reprogramming factors directly to astrocytes in a monkey model of PD.

This project is funded, in part, under a grant with the Pennsylvania Department of Health (PDH). The PDH specifically disclaims responsibility for any analyses, interpretations, or conclusions. Additional support was provided by the Penn Institute for Regenerative Medicine. Co-authors, in addition to Gearhart and Addis, are Rebecca L. Wright and Marc A. Dichter from Penn and Fu-Chun Hsu and Douglas A. Coulter, from the Children’s Hospital of Philadelphia.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.

Penn's Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>