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 Penn studies find promise for innovations in liquid biopsies
30.03.2017 | University of Pennsylvania School of Medicine

nachricht 'On-off switch' brings researchers a step closer to potential HIV vaccine
30.03.2017 | University of Nebraska-Lincoln

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: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>