Navigation Links
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 i n 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 a s 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.


'"/>

Source:University of California - San Francisco


Related biology news :

1. Genome of deadly amoeba shows surprising complexity, evidence of lateral gene transfer
2. “Nano-scissors?laser shows precise surgical capability
3. Clam embryo study shows pollutant mixture adversely affects nerve cell development
4. New imaging method gives early indication if brain cancer therapy is effective, U-M study shows
5. Study shows nanoshells ideal as chemical nanosensors
6. Gene vaccine for Alzheimers disease shows promising results
7. Flocking together: Study shows how animal groups find their way
8. New drug shows promise as powerful anticancer agent
9. Loves all in the brain: fMRI study shows strong, lateralized reward, not sex, drive
10. Test for early detection of prostate cancer shows promise
11. Mouse gene shows new mechanism behind cardiac infarction in man
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/31/2016)... March 31, 2016   ... or the "Company") LegacyXChange is excited to ... its soon to be launched online site for trading ... ) will also provide potential shareholders a sense ... technology to an industry that is notorious for fraud. ...
(Date:3/29/2016)... BOCA RATON, Florida , March 29, 2016 /PRNewswire/ ... ("LegacyXChange" or the "Company") LegacyXChange "LEGX" and SelectaDNA/CSI Protect ... Synthetic DNA in ink used in a variety of ... preventing theft. Buyers of originally created collectibles from athletes ... authenticity through forensic analysis of the DNA. ...
(Date:3/22/2016)... India , March 22, 2016 /PRNewswire/ ... market research report "Electronic Sensors Market for Consumer ... Proximity, & Others), Application (Communication & IT, ... Geography - Global Forecast to 2022", published ... industry is expected to reach USD 26.76 ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... Supplyframe, the Industry ... Supplyframe Design Lab . Located in Pasadena, Calif., the Design Lab’s mission ... hardware projects are designed, built and brought to market. , The Design Lab ...
(Date:6/23/2016)... 2016  Blueprint Bio, a company dedicated to identifying, ... community, has closed its Series A funding round, according ... "We have received a commitment from Forentis Fund ... to meet our current goals," stated Matthew Nunez ... to complete validation on the current projects in our ...
(Date:6/23/2016)... ... June 23, 2016 , ... Regulatory Compliance Associates® ... provides a free webinar on Performing Quality Investigations: Getting to Root ... CT at no charge. , Incomplete investigations are still a major concern to ...
(Date:6/22/2016)... 22, 2016 Cell Applications, Inc. and ... to produce up to one billion human induced ... one week. These high-quality, consistent stem cells enable ... and spend more time doing meaningful, relevant research. ... high-volume manufacturing process that produces affordable, reliable HiPSC ...
Breaking Biology Technology: