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.
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.
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!
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences