Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Test reveals effectiveness of potential Huntington's disease drugs

31.10.2006
A test using cultured cells provides an effective way to screen drugs against Huntington's disease and shows that two compounds - memantine and riluzole — are most effective at keeping cells alive under conditions that mimic the disorder, UT Southwestern Medical Center researchers report.

"These drugs have been tested in a variety of Huntington's disease models and some HD human trials and results are very difficult to interpret," said Dr. Ilya Bezprozvanny, associate professor of physiology and senior author of the study, available online and published in today's issue of Neuroscience Letters. "For some of these drugs conflicting results were obtained by different research groups, but it is impossible to figure out where the differences came from because studies were not conducted in parallel.

"We systematically and quantititatively tested the clinically relevant drugs side-by-side in the same HD model. That has never been done before," said Dr. Bezprozvanny.

Huntington's disease is a fatal genetic disorder, manifesting in adulthood, in which certain brain cells die. The disease results in uncontrolled movements, emotional disturbance and loss of mental ability. The offspring of a person with Huntington's have a 50 percent chance of inheriting it.

... more about:
»Disease »Huntington' »glutamate »memantine

More than 250,000 people in the United States have the disorder or are at risk for it. There is no cure, but several drugs are used or are being tested to relieve symptoms or slow Huntington's progression.

The disease affects a part of the brain called the striatum, which is involved in the control of movement and of "executive function," or planning and abstract thinking. It primarily attacks nerve cells called striatal medium spiny neurons, the main component of the striatum.

Dr. Bezprozvanny's group previously demonstrated that Huntington's striatal neurons are oversensitive to glutamate, a compound that nerve cells use to communicate with each other.

In the latest UT Southwestern study, the researchers cultured striatal spiny neurons from the brains of mice genetically engineered to express the mutant human Huntington gene. As predicted, glutamate killed the Huntington's neurons, but the scientists also tested five clinically relevant glutamate inhibitors to assess their protective ability.

Folic acid has been suggested as a treatment for people with Huntington's because it interacts with homocysteine, a compound that makes nerve cells more vulnerable to glutamate. Gabapentin and lamotrigine, both glutamate inhibitors, are used in epilepsy treatment and as a mood stabilizer, respectively. These three compounds did not significantly protect the cultured cells.

However, a drug called memantine, which is used to treat Alzheimer's disease, and riluzole, used in amyotrophic lateral sclerosis, did protect the cells. Memantine demonstrated a stronger effect in the study. Memantine has also shown evidence of retarding the progression of Huntington's in people, while riluzole has helped relieve some symptoms.

"Our results provide the first systematic comparison of various clinically relevant glutamate pathway inhibitors for HD treatment and indicate that memantine holds the most promise based on its in vitro efficacy," Dr. Bezprozvanny said. "Whole animal studies of memantine in an HD mouse model will be required to validate these findings."

Other UT Southwestern researchers involved in the study were Drs. Jun Wu, research associate in physiology, and Tie-Shan Tang, instructor in physiology.

The work was supported by the Robert A. Welch Foundation, the High Q Foundation and the National Institute for Neurological Diseases and Stroke.

Aline McKenzie | EurekAlert!
Further information:
http://www.utsouthwestern.edu

Further reports about: Disease Huntington' glutamate memantine

More articles from Life Sciences:

nachricht Cnidarians remotely control bacteria
21.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Immune cells may heal bleeding brain after strokes
21.09.2017 | NIH/National Institute of Neurological Disorders and Stroke

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Comet or asteroid? Hubble discovers that a unique object is a binary

21.09.2017 | Physics and Astronomy

Cnidarians remotely control bacteria

21.09.2017 | Life Sciences

Monitoring the heart's mitochondria to predict cardiac arrest?

21.09.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>