Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Combination of gene therapy and gene silencing prevents neurodegenerative disease

05.07.2004


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 May, where it was nominated the top abstract.

Jennifer Brown | EurekAlert!
Further information:
http://www.uiowa.edu
http://www.uihealthcare.com

More articles from Health and Medicine:

nachricht Finding new clues to brain cancer treatment
21.02.2020 | Case Western Reserve University

nachricht UIC researchers find unique organ-specific signature profiles for blood vessel cells
18.02.2020 | University of Illinois at Chicago

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: High-pressure scientists in Bayreuth discover promising material for information technology

Researchers at the University of Bayreuth have discovered an unusual material: When cooled down to two degrees Celsius, its crystal structure and electronic properties change abruptly and significantly. In this new state, the distances between iron atoms can be tailored with the help of light beams. This opens up intriguing possibilities for application in the field of information technology. The scientists have presented their discovery in the journal "Angewandte Chemie - International Edition". The new findings are the result of close cooperation with partnering facilities in Augsburg, Dresden, Hamburg, and Moscow.

The material is an unusual form of iron oxide with the formula Fe₅O₆. The researchers produced it at a pressure of 15 gigapascals in a high-pressure laboratory...

Im Focus: From China to the South Pole: Joining forces to solve the neutrino mass puzzle

Study by Mainz physicists indicates that the next generation of neutrino experiments may well find the answer to one of the most pressing issues in neutrino physics

Among the most exciting challenges in modern physics is the identification of the neutrino mass ordering. Physicists from the Cluster of Excellence PRISMA+ at...

Im Focus: Therapies without drugs

Fraunhofer researchers are investigating the potential of microimplants to stimulate nerve cells and treat chronic conditions like asthma, diabetes, or Parkinson’s disease. Find out what makes this form of treatment so appealing and which challenges the researchers still have to master.

A study by the Robert Koch Institute has found that one in four women will suffer from weak bladders at some point in their lives. Treatments of this condition...

Im Focus: A step towards controlling spin-dependent petahertz electronics by material defects

The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.

Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

Turbomachine expander offers efficient, safe strategy for heating, cooling

25.02.2020 | Power and Electrical Engineering

The seismicity of Mars

25.02.2020 | Earth Sciences

Cancer cachexia: Extracellular ligand helps to prevent muscle loss

25.02.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>