"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 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!
Chains of nanogold – forged with atomic precision
23.09.2016 | Suomen Akatemia (Academy of Finland)
Self-assembled nanostructures hit their target
23.09.2016 | King Abdullah University of Science and Technology
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...
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...
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...
At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.
In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...
Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.
K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...
23.09.2016 | Event News
20.09.2016 | Event News
16.09.2016 | Event News
23.09.2016 | Life Sciences
23.09.2016 | Health and Medicine
23.09.2016 | Life Sciences