Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene Therapy Prevents Neurodegenerative Disease

07.07.2004


University of Iowa researchers have shown for the first time that gene therapy delivered to the brains of living mice can prevent the physical symptoms and neurological damage caused by an inherited neurodegenerative disease that is similar to Huntington’s disease (HD).



If the therapeutic approach can be extended to humans, it may provide a treatment for a group of incurable, progressive neurological diseases called polyglutamine-repeat diseases, which include HD and several spinocerebellar ataxias. The study, conducted by scientists at the UI Roy J. and Lucille A. Carver College of Medicine and colleagues at the University of Minnesota and the National Institutes of Health (NIH), appears in the August issue of Nature Medicine and in the journal’s advanced online publication July 4.

"This is the first example of targeted gene silencing of a disease gene in the brains of live animals and it suggests that this approach may eventually be useful for human therapies," said senior study author Beverly Davidson, Ph.D., the Roy J. Carver Chair in Internal Medicine and UI professor of internal medicine, physiology and biophysics, and neurology. "We have had success in tissue culture, but translating those ideas to animal models of disease has been a barrier. We seem to have broken through that barrier."


Davidson and her colleagues used a viral vector (a stripped-down virus) to deliver small fragments of genetic material (RNA) to critical brain cells of mice with a disorder that mimics the human neurodegenerative disease spinocerebellar ataxia 1 (SCA1). The genetic material suppresses the disease-causing SCA1 gene in a process known as RNA interference.

Mice with the SCA1 gene that were treated with the gene therapy had normal movement and coordination. The gene therapy also protected brain cells from the destruction normally caused by the disease and prevented the build-up of protein clumps within the cells. In contrast, mice with the SCA1 disease gene that were not treated developed movement problems and lost brain cells in a manner similar to humans with this condition.

Both SCA1 and Huntington’s disease are members of a group of neurodegenerative disorders caused by a particular type of genetic flaw. In these dominantly inherited diseases, a single mutated gene inherited from either parent produces a protein that is toxic to cells. Thus, a successful therapy must remove or suppress the disease-gene rather than simply add a corrected version.

"Although we know how to put genes into cells, the difficulty we face in treating dominant diseases is how to remove or silence genes," Davidson explained. "With our approach we can marry our gene therapy research using viral vectors with RNA interference."

Silencing the SCA1 gene with RNA interference inhibited the production of a neurotoxic protein, suggesting that this technology may also be helpful against other degenerative neurological diseases caused by neurotoxic proteins, such as Alzheimer’s disease.

In addition to the finding that RNA interference inhibited gene expression to such an extent that it protected the animals against the disease, another important finding was that RNA interference in and of itself does not appear to be toxic to normal brain cells. In the UI study, neither animal behavior nor brain structures were adversely affected by RNA interference gene therapy.

Furthermore, the study revealed that specific properties of different gene therapy vectors can be used to target those cells that are most involved in causing the disease symptoms. In this case, the UI team proved that their gene therapy vector, adeno-associated virus 1, specifically targeted Purkinje cells, which are very important for gait and coordination.

"Choosing the right vector for the right cells could help us limit gene expression to those cells where altering expression will have a beneficial effect," Davidson explained.

Davidson is optimistic about the potential for using RNA interference gene therapy to treat neurological diseases like HD and spinocerebellar ataxias in humans.

"This is among the most important work I have done and I am excited about the prospect of helping to move this approach into clinical trials," she added.

In addition to Davidson, the team included UI researchers: Haibin Xia, Ph.D., and Qinwen Mao, Ph.D., who were co-lead authors of the study; Henry Paulson, M.D., Ph.D.; Steven Eliason; Scott Harper, Ph.D.; and Inês Martins. Harry Orr, Ph.D., at the University of Minnesota, and Linda Yang and Robert Kotin, Ph.D., at the NIH also were part of the team.

Davidson first presented these findings at the American Society of Gene Therapy meeting in June, where it was nominated the top abstract.

The study was funded in part by the NIH, the Hereditary Disease Foundation and the Roy J. Carver Charitable Trust.

| newswise
Further information:
http://www.uihealthcare.com
http://www.uiowa.edu

More articles from Life Sciences:

nachricht Lethal combination: Drug cocktail turns off the juice to cancer cells
12.12.2018 | Universität Basel

nachricht Smelling the forest – not the trees
12.12.2018 | Universität Konstanz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

New discoveries predict ability to forecast dementia from single molecule

12.12.2018 | Health and Medicine

CCNY-Yale researchers make shape shifting cell breakthrough

12.12.2018 | Physics and Astronomy

Pain: Perception and motor impulses arise in the brain independently of one another

12.12.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>