Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene therapy success in the laboratory buoys hope for Parkinson’s disease

11.10.2002


Scientists at Jefferson Medical College have used gene therapy to reverse the progression of Parkinson’s disease in rats. They have found that by adding a gene for an enzyme, they were able to reprogram brain circuitry and halt the deterioration of dopamine producing brain cells, one of the key problems in the disease.



“It’s not just inserting a replacement for a missing or mutated gene as a treatment for a genetic disorder,” says Michael Oshinsky, Ph.D., research assistant professor of neurology at Jefferson Medical College of Thomas Jefferson University in Philadelphia and part of the team reporting its results October 11 in the journal Science. “This is more profound. We are actually changing the brain’s circuitry as treatment for a disease.”

According to Dr. Oshinsky and Jia Luo, M.D., research associate at Jefferson Medical College of Thomas Jefferson University, in Parkinson’s, a portion of the brain called the subthalamic nucleus is overactive. These cells produce glutamate, an excitatory neurotransmitter, or chemical message carrier, into another region called the substantia nigra, which is important for the coordination of movement and where the brain chemical dopamine is made. Parkinson’s is caused by the deterioration of dopamine-producing nerve cells.


The researchers – including scientists from Jefferson, the University of Auckland, New Zealand, and Cornell University – took their cues from work with deep brain stimulation, where brain cells in the subthalamic nucleus are stimulated at a high frequency as a treatment for late-stage Parkinson’s. This treatment prevents overactivity in the substantia nigra.

The team, led by Matthew During, M.D., formerly of Jefferson Medical College of Thomas Jefferson University and now at the University of Auckland, decided that instead of turning off the neurons in the subthalamic nucleus, they would attempt to change the neurons from excitatory to inhibitory, which would then contain the inhibitory chemical messenger GABA.

The team used an adeno-associated virus to carry the gene for an enzyme, glutamic acid decarboxylase (GAD), into brain cells in rats that were made Parkinsonian. They saw a dramatic difference in the behavior and physiology of the Parkinsonian rats treated with the GAD-carrying virus compared to the Parkinsonian rats that did not receive the treatment.

Three weeks after the gene transfer, Dr. Luo made Parkinson’s lesions on one side of the brains of rats that had the gene therapy. The researchers then performed various behavioral tests to see if the gene therapy could protect against the development of classic Parkinson’s symptoms. One test showed that nearly 70 percent of the animals with Parkinson’s lesions and the GAD gene therapy had no Parkinson’s symptoms when they received chemicals that mimicked dopamine in the brain. Normally, animals with Parkinson’s are hypersensitive to dopamine, and actually respond to it by running around in circles over and over. The test result was a “very strong behavioral measure showing this is a good treatment for Parkinson’s,” Dr. Oshinsky says.

The researchers also stimulated the rats’ subthalamic nucleus and examined the resulting connection in the substantia nigra. They compared animals that had received the GAD gene therapy with those that had not had the gene therapy and normal rats. In the untreated Parkinsonian rats, more than 80 percent of cells showed excitatory responses. As few as 10 percent showed inhibitory responses.

But in the GAD-treated animals, they found practically the opposite. Nearly 80 percent of the neurons they recorded signals from showed inhibitory responses, whereas only about 17 percent showed excitatory responses. “It was a profound change in the connection between the subthalamic nucleus and the substantia nigra – that’s where there was a phenotypic change in the neural connections,” Dr. Oshinsky explains.

“By reprogramming it [the brain’s circuitry], we actually could show that it was protecting dopamine neurons from dying off,” Dr. During says. “The main advantage is that inhibitory input seems to protect the dopamine neurons.”

“It’s a classic excitatory connection in the brain and we converted it to an inhibitory connection,” Dr. Oshinsky says. “It’s nice to be able to show a real mechanism of action for a potential treatment of Parkinson’s.” He notes that the rats were tested as many as 10 months after receiving gene therapy; the change was permanent. The group already has approval from the Food and Drug Administration for a clinical trial, which will be the first gene therapy protocol for Parkinson’s disease.

Steve Benowitz | EurekAlert!
Further information:
http://www.tju.edu/

More articles from Health and Medicine:

nachricht Custom-tailored strategy against glioblastomas
26.09.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: New welding process joins dissimilar sheets better

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

HLF: From an experiment to an establishment

29.09.2016 | Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

Laser use for neurosurgery and biofabrication - LaserForum 2016 focuses on medical technology

27.09.2016 | Event News

 
Latest News

New Multiferroic Materials from Building Blocks

29.09.2016 | Materials Sciences

Silicon Fluorescent Material Developed Enabling Observations under a Bright “Biological Optical Window”

29.09.2016 | Materials Sciences

X-shape Bio-inspired Structures

29.09.2016 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>