Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Old drug shows new promise for Huntington’s Disease


Clioquinol, an antibiotic that was banned for internal use in the United States in 1971 but is still used in topical applications, appears to block the genetic action of Huntington’s disease in mice and in cell culture, according to a study reported by San Francisco VA Medical Center (SFVAMC) researchers.

The study, led by principal investigator Stephen M. Massa, MD, PhD, a neurologist at SFVAMC, was reported in the August 16, 2005 issue of Proceedings of the National Academy of Sciences.

Huntington’s disease is a hereditary, degenerative, and ultimately fatal disease of the brain that causes changes in personality, progressive loss of memory and cognitive ability, and a characteristic uncontrolled jerking motion known as Huntington’s chorea. There is no known cure or effective treatment. A person who carries the mutant Huntington’s gene may pass it on unknowingly because the disease often manifests in early to late middle age after the carrier’s children have already been born.

During the course of the disease, the Huntington’s gene causes the production of a toxic protein, mutant huntingtin, in neurons (brain cells). Eventually the protein kills the neurons, causing the disease’s degenerative effects.

In Massa’s study, Clioquinol appeared to interrupt the production of mutant huntingtin. In the first part of his study, Massa and his research team tested the effect of Clioquinol on neurons in cell culture that contained a form of the mutant Huntington’s gene. "We found that not only did cells look better and survive a bit longer when exposed to the drug, but they also seemed to make less of the toxic protein," observed Massa, who is also a clinical assistant professor of neurology at the University of California, San Francisco (UCSF).

Based on the in vitro results, Massa decided to test the drug in vivo, on mice bred to express the toxic huntingtin protein. The mice were given approximately 1 milligram of Clioquinol per day in water. After eight weeks of treatment, they had accumulated four times less toxic protein in their brains than control mice given water alone. The experimental animals lived 20 percent longer than the control animals, did better on tests of motor coordination, and had less weight loss.

"It’s a limited study, in that we used the same drug dose on all the animals as opposed to comparing different doses, but fairly convincing," Massa concluded. "Together, the in vitro and in vivo results suggest that Clioquinol has an effect of decreasing the symptoms of Huntington’s, its pathology, and perhaps even the actual production of the toxic protein."

However, he noted, "the drug’s mechanism of action remains unclear." The clearer the mechanism of the drug, he explained, the better the chance that researchers might eventually be able to create a medication that is both safe and effective.

Like some other antibiotics, Clioquinol is known to be a chelator -- that is, it binds metals in body tissues, particularly copper and zinc, and removes them when it is excreted. Massa and other researchers believe that this chelation effect may interfere with production of the mutant huntingtin protein in some way. "But there are still a couple of explanations we need to rule out," he said.

To that end, Massa’s next studies will involve the creation of an in vitro system in which toxic and non-toxic forms of huntingtin are made in the same cell. He and his team will then evaluate the effects of Clioquinol on several phases of protein synthesis within the cell. Massa hopes these experiments will confirm initial indications that Clioquinol preferentially interferes with synthesis of the toxic form of the protein. "Then we can move on to trying to isolate the actual mechanism of the drug," he predicted.

"However," Massa cautioned, "the record of successfully translating drugs from animal to human use is not good."

Clioquinol has shown promise as a potential treatment for Alzheimer’s disease in recent studies in mice and humans. Apparently through chelation, it interferes with the creation of beta-amyloid plaque in the brain, which has been implicated in the progression of Alzheimer’s symptoms.

Currently, Clioquinol is banned for internal use in many countries because of its side effects. In Japan in the late 1950s and 60s, the drug was found to cause a neurologic condition called subacute myelo-optico-neuropathy (SMON), with symptoms including visual loss, muscle weakness, and numbness, in several thousand people. However, noted Massa, the doses given in current clinical trials are much smaller than were commonly prescribed in Japan. In addition, he explained, it has been found that vitamin B12, when taken along with the drug, protects against its potential toxic effects.

Co-authors of the study were Trent Nguyen, PhD, and Aaron Hamby, BS, of SFVAMC and UCSF.

Steve Tokar | EurekAlert!
Further information:

More articles from Studies and Analyses:

nachricht Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University

nachricht New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

A new kind of quantum bits in two dimensions

19.03.2018 | Physics and Astronomy

Scientists have a new way to gauge the growth of nanowires

19.03.2018 | Materials Sciences

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Science & Research
Overview of more VideoLinks >>>