Featured Research

from universities, journals, and other organizations

Huntington's Disease: Italian Discovery May Suggest A New Approach For Developing Therapies

Date:
June 21, 2001
Source:
American Association For The Advancement Of Science
Summary:
Like a good parent, a protein called huntingtin helps to safeguard key nerve cells in the brain. When the huntingtin protein is defective, however, certain neurons can become damaged, resulting in Huntington's Disease, a debilitating and fatal form of brain degeneration characterized by physical, mental and emotional disturbances. The discovery of one of normal huntingtin's exact functions within the brain suggests novel therapeutic strategies to fight the disorder.

Like a good parent, a protein called huntingtin helps to safeguard key nerve cells in the brain. When the huntingtin protein is defective, however, certain neurons can become damaged, resulting in Huntington's Disease, a debilitating and fatal form of brain degeneration characterized by physical, mental and emotional disturbances.

Related Articles


The discovery of one of normal huntingtin's exact functions within the brain--to be published online by the journal, Science, as part of the Science Express web site on 14 June--suggests novel therapeutic strategies to fight the disorder.

"Much additional research must be completed before these findings can help patients, and we want to be clear that this is not a cure," researcher Elena Cattaneo of the University of Milan emphasized. "But, we're optimistic that our work will help guide the development of new therapies, such as drugs to replace or boost the activity of normal huntingtin, or to increase levels of another brain protein, BDNF."

Cattaneo's research was supported mainly by Telethon Italy, and by the Huntington's Disease Society of America, two non-profit organizations.

A primarily hereditary disorder of the central nervous system, the prevalence of Huntington's Disease ranges from one in every 10,000 individuals in Europe and the United States, to seven of every 1,000 in Venezuela, said Cattaneo, who directed the international Science study team. In Italy, an estimated 4,000 individuals are affected, and another 12,000 carry the disease gene but have not yet developed symptoms.

Symptoms range from uncontrollable muscular movements to memory lapses, difficulty with swallowing, and behavioral or psychological changes. Striking most often in mid-adulthood, between ages 30 and 50, the disease progresses toward death within 15 to 20 years.

Huntington's Disease has been traced to a defective gene on chromosome 4, which produces the huntingtin protein, discovered in 1993. Previous research has shown that the mutation of huntingtin launches the protein into overdrive, a state described by scientists as a toxic "gain-of function," resulting in neuronal cell death.

While the hyperactivity of mutant huntingtin may account for some aspects of the disease, Cattaneo's team has revealed, it's largely the loss of "good parenting," through the mutation of huntingtin, that leaves neurons vulnerable to damage. Huntingtin's normal function, researchers show, is to regulate the transcription of the BDNF protein, which is essential for the survival of neurons located within the striatum. This transcription is impaired with mutant huntingtin, resulting in lowered levels of neuron-protecting BDNF.

"We believe that the loss of huntingtin's beneficial functions contributes to the disease," said Cattaneo.

Researchers examined normal huntingtin's function in cultured cells and laboratory animals. First, they produced striatal cells that expressed either normal or mutant huntingtin. Then, they measured the cells' production of certain biochemicals, called neurotrophins, which help neurons survive. Cells expressing normal huntingtin had high levels of the neurotrophin, BDNF, whereas this effect was lost in cells expressing the mutant protein.

To survive, adult neurons in the brain's striatum must receive BDNF produced within the cerebral cortex. In transgenic mice expressing normal huntingtin, Cattaneo reported, BDNF proceeded via the usual pathway, from the cortex to the striatum. But, this delivery system was disturbed in mice expressing mutant huntingtin, as less BDNF was generated in the cortex. These findings were further confirmed by dose-dependent tests, and by the post-mortem analysis of a human brain afflicted by Huntington's Disease: Evidence of reduced BDNF transcription was found in the cortex, with subsequently reduced levels of the neurotrophin in the striatum.

Cattaneo speculates that similar "loss-of-function" mechanisms may play a role in seven other neurodegenerative diseases.

Efforts to treat Huntington's Disease have so far ranged from experimental fetal-cell transplants to neuron-protecting agents and antipsychotic or antidepressant medications. Other strategies include, for example, the use of an antibiotic that blocks the production of two enzymes known to fragment mutant huntingtin, producing toxic effects in cells.

"There will be no drug ready tomorrow, based on this research," Cattaneo said. "But, now we have a new idea for how to develop therapies, perhaps in the very close future. Before treatments can be proposed, we need to understand exactly how huntingtin speaks to the BDNF gene to increase its activity. We believe this research will progress very rapidly over the next few months. As a next step, trials are under development to deliver BDNF via gene therapy to HD transgenic mice."

With Cattaneo, authors on the Science paper include Chiara Zuccato, Andrea Ciammola, Dorotea Rigamonti, Donato Goffredo, Luciano Conti, Simonetta Sipione, and Vincenzo Silani, all of the University of Milan; as well as Blair R. Leavitt and Michael R. Hayden of the University of British Columbia; Marcy E. MacDonald of Massachusetts General Hospital; Robert M. Friedlander of Brigham and Women's Hospital; and Tonis Timmusk of the Institute of Biotechnology in Finland. [Zuccato et al., "Loss of Huntingtin-Mediated BDNF Gene Transcription in Huntington's Disease."]


Story Source:

The above story is based on materials provided by American Association For The Advancement Of Science. Note: Materials may be edited for content and length.


Cite This Page:

American Association For The Advancement Of Science. "Huntington's Disease: Italian Discovery May Suggest A New Approach For Developing Therapies." ScienceDaily. ScienceDaily, 21 June 2001. <www.sciencedaily.com/releases/2001/06/010615072159.htm>.
American Association For The Advancement Of Science. (2001, June 21). Huntington's Disease: Italian Discovery May Suggest A New Approach For Developing Therapies. ScienceDaily. Retrieved October 30, 2014 from www.sciencedaily.com/releases/2001/06/010615072159.htm
American Association For The Advancement Of Science. "Huntington's Disease: Italian Discovery May Suggest A New Approach For Developing Therapies." ScienceDaily. www.sciencedaily.com/releases/2001/06/010615072159.htm (accessed October 30, 2014).

Share This



More Mind & Brain News

Thursday, October 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Techy Tots Are Forefront of London's Baby Show

Techy Tots Are Forefront of London's Baby Show

AP (Oct. 28, 2014) Moms and Dads get a more hands-on approach to parenting with tech-centric products for raising their little ones. (Oct. 28) Video provided by AP
Powered by NewsLook.com
Cocoa Could Be As Good For Memory As It Is For A Sweet Tooth

Cocoa Could Be As Good For Memory As It Is For A Sweet Tooth

Newsy (Oct. 27, 2014) Researchers have come up with another reason why dark chocolate is good for your health. A substance in the treat can reportedly help with memory. Video provided by Newsy
Powered by NewsLook.com
Five-Year-Olds Learn Coding as Britain Eyes Digital Future

Five-Year-Olds Learn Coding as Britain Eyes Digital Future

AFP (Oct. 27, 2014) Coding has become compulsory for children as young as five in schools across the UK. Making it the first major world economy to overhaul its IT teaching and put programming at its core. Duration: 02:19 Video provided by AFP
Powered by NewsLook.com
Academic Scandal Shocks UNC

Academic Scandal Shocks UNC

AP (Oct. 23, 2014) A scandal involving bogus classes and inflated grades at the University of North Carolina was bigger than previously reported, a new investigation found. (Oct. 23) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins