Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A step toward controlling Huntington's disease?

24.06.2011
Johns Hopkins researchers identify a potential new way of blocking activity of gene that causes HD

Johns Hopkins researchers have identified a natural mechanism that might one day be used to block the expression of the mutated gene known to cause Huntington’s disease. Their experiments offer not an immediate cure, but a potential new approach to stopping or even preventing the development of this relentless neurodegenerative disorder.

Huntington’s disease is a rare, fatal disorder caused by a mutation in a single gene and marked by progressive brain damage. Symptoms, which typically first appear in midlife, include jerky twitch-like movements, coordination troubles, psychiatric disorders and dementia. Although the gene responsible for Huntington’s was identified in 1993, there is no cure, and there are no treatments are available even to slow its progression.

The disorder is caused by a mutation in the huntingtin gene (HTT). The mutation occurs when a section of DNA, which normally varies in length from one person to another, is too long. The result is the production of an abnormal and toxic version of the huntingtin protein. The mutation has a second unfortunate effect, the Johns Hopkins researchers discovered — it reduces a natural braking mechanism that might otherwise keep the amount of toxic huntingtin protein in check and keep the disease from developing.

“The idea of being able to harness the powers of this natural mechanism for the benefit of Huntington’s patients is a totally new way of thinking about therapy for the disease,” says Russell L. Margolis, M.D., a professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and leader of the team publishing results of the study online in the journal Human Molecular Genetics.

Currently, a leading strategy among Huntington’s disease researchers is to try to suppress the expression of the mutant gene by introducing fragments of DNA meant to bind with and sabotage the ability of the gene to make the damaging protein. The goal of this approach is to prevent the mutant HTT from being expressed in the brain and potentially slow, if not stop, the disease’s march. Although cell and animal models have shown promise, Margolis and other researchers worry that getting just the right amount of DNA into the right portions of the brain may be a difficult or risky task, likely involving injections into cerebral spinal fluid or the brain itself. The feasibility of this approach remains unknown, he adds.

The new study suggests an alternative focus — manipulating the newly identified natural “brake” with a drug so that more of the brake is made, which can then specifically stop or slow production of the huntingtin protein. “Whether it’s possible to do this and do it safely remains to be seen,” Margolis says, “but this gives us another approach to explore.”

On the strand of DNA opposite the huntingtin gene, the researchers found another gene, which they named huntingtin antisense. This gene also includes the Huntington’s disease mutation. In normal brain tissue and in cells growing in the laboratory without the Huntington’s disease mutation, Margolis and his team determined that huntingtin antisense acts to inhibit the amount of huntingtin gene that is expressed. But in brain tissue and cells with the Huntington’s disease mutation, there is less huntingtin antisense gene expressed, so the biochemical foot is essentially taken off the brake, leaving a toxic amount of huntingtin protein. Reapplying the brake, by experimentally altering cells grown in culture so that they express a large amount of huntingtin antisense, decreased the amount of the toxic huntingtin protein.

Huntington’s disease was first described in the medical literature in 1872, but it wasn’t until 1993 that the gene mutation was discovered “with hopes that the discovery would quickly lead to treatment,” Margolis says. But the disease has proven unexpectedly complicated, with dozens of different pathways implicated as potential causes of cell damage and death, he adds.

People with a single copy of the mutated gene will get Huntington’s disease, which afflicts roughly 30,000 people in the United States. “It is a terrible disease in which family members can find out what’s coming and are just waiting for the symptoms to present themselves,” Margolis says. “We need to find ways to help them.”

This study was funded by the National Institutes of Health.

Other Hopkins researchers involved in the study include Daniel W. Chung, M.A.; Dobrila D. Rudnicki , Ph.D.; and Lan Yu, Ph.D.

For more information:

http://www.hopkinsmedicine.org/psychiatry/specialty_areas/huntingtons_disease/

Stephanie Desmon | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Health and Medicine:

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>