Navigation Links
A step toward controlling Huntington's disease?
Date:6/23/2011

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."


'/>"/>

Contact: Stephanie Desmon
sdesmon1@jhmi.edu
410-955-8665
Johns Hopkins Medical Institutions
Source:Eurekalert

Related medicine news :

1. Toward a more efficient therapy for a specific form of leukemia
2. Attitudes toward end-of-life care: A survey of cancer patients and others in Korea
3. NIH grant for the move toward clinical trials targeting the lysosomal storage disease MPSIIIB
4. U.S. Pushes School Cafeterias Toward Healthier Offerings
5. Toward a vaccine for methamphetamine abuse
6. Negative attitudes toward fat bodies going global, study finds
7. Tiny gems take big step toward battling cancer
8. Top scientists unite to develop global scientific strategy Towards An HIV Cure
9. Toward a fast, simple test for detecting cholera rampaging in 40 countries
10. Major step taken toward an open and shared digital brain atlasing framework
11. Warning about benevolent sexism and mens apparently positive attitudes towards women
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/2/2016)... ... December 02, 2016 , ... Center for Autism and Related Disorders (CARD) ... by autism spectrum disorder (ASD) and other developmental disabilities. The group, which is being ... and other caregivers the opportunity to share stories and advice, seek help, and continue ...
(Date:12/2/2016)... ... 02, 2016 , ... Dr. Raffi Hovsepian, a leading plastic, ... 2016 “Guide to America’s Top Plastic Surgeons” for seven consecutive years. The prestigious ... experience, and professional associations. , One the most frequently honored surgeons in ...
(Date:12/2/2016)... ... December 02, 2016 , ... Universal Medical ... systems and the first company to offer robotic imaging to veterinary medicine is ... booth # 941 for the American Association of Equine Practitioners 62nd Annual Convention ...
(Date:12/2/2016)... San Francisco, CA (PRWEB) , ... December 02, ... ... in digitally-enabled care journeys, announced today that it has raised $6.0 million in ... are inspired by Clarify Health’s conviction that patients and their caregivers can receive ...
(Date:11/30/2016)... Massachusetts (PRWEB) , ... November 30, 2016 , ... ... proud to announce that we have been designated as a Cigna Infertility Center ... or exceed rigorous performance standards. , “It’s an honor to be designated ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... , Dec. 1, 2016  Today, Simpson Healthcare Executives, ... honor of being selected as winners of multiple awards ... Executives Website at the PLATINUM level, Blue Zones Menu ... at the GOLD Level, and our proprietary 3ConneX Platform ... Simpson Healthcare Executives, we are excited to showcase our ...
(Date:12/2/2016)... Allergan plc (NYSE: AGN ), a ... previously announced Accelerated Share Repurchase (ASR) Program. Logo - ... ... previously announced, the Company entered into a variable tenor ASR ... repurchase $10 billion of its ordinary shares. Approximately 40.5 million ...
(Date:11/30/2016)... 2016 Research and Markets has announced the ... MedCore" report to their offering. ... , Detachable coil embolization is ... malformations. The detachable coil embolization treatment of cerebral aneurysms is less invasive ... weakened area in the wall of an artery in the brain. This ...
Breaking Medicine Technology: