Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeting a key enzyme with gene therapy reversed course of Alzheimer’s disease in mouse models

22.09.2005


Silencing Alzheimer’s: targeting a key enzyme with gene therapy reversed course of disease in mouse models



In mice, that had been genetically engineered to develop Alzheimer’s disease, scientists were able to reverse the rodents’ memory loss by reducing the amount of an enzyme that is crucial for the development of Alzheimer’s disease.

"What we are showing is a proof of principle that stopping the synthesis of a protein that is necessary for the formation of the telltale plaques reverses the progression of the disease, and more importantly, the cognitive function of these mice, which had already been impaired, has now recovered," says Inder Verma, professor in the Laboratory for Genetics at the Salk Institute for Biological Studies.


The findings, which are the result of a close collaboration between researchers at the Salk Institute and scientists at the University of California in San Diego, are reported in an advance on-line publication of Nature Neuroscience.

In the past, gene therapy has been mainly used to deliver normal genes into cells to compensate for defective versions of the gene causing disease. In their study, the researchers used gene therapy to silence a normally functioning gene. Exploiting a mechanism called RNA interference, they were able to turn down the gene that helps produce the characteristic amyloid plaques that are one of the hallmarks of Alzheimer’s disease.

"Within a month of treatment, mice that had already suffered memory deficits could learn and remember how to find their way through a water maze," says co-author Robert Marr, a post-doctoral researcher in Verma’s lab.

"It appears that these mice can come back from a very severe level of disease progression," adds first author Oded Singer, also at the Salk. "This is a very important finding because humans are usually diagnosed when the disease has already progressed relatively far."

But he warns that it is too early to make direct comparisons with the human disease, since mice ordinarily don’t develop the symptoms of the disease unless they are genetically engineered to do so.

Amyloid plaques, which are insoluble protein clumps in the brain, can precede the onset of dementia by many years. These plaques are formed when enzymes cleave the amyloid precursor protein (APP) releasing the toxic beta amyloid fragments that clump together to form the sticky plaques. One of the enzymes doing the cleaving is called beta secretase or BACE1.

And although the production of beta amyloid occurs in all brains, healthy brains are able to clear away excess amounts. Brains of people with Alzheimer’s disease, on the other hand, are unable to control beta amyloid accumulation.

For several years now, drug companies have been trying to find a drug that inhibits BACE1 and thus prevent beta amyloid from building up in brains of people with Alzheimer’s disease. But so far, the goal has remained elusive.

Instead of looking for chemical compounds to inhibit BACE1, Oded Singer, collaborating with the laboratories of Fred H. Gage at the Salk Institute and lead author Eliezer Masliah at UCSD, resorted to small biological molecules, called short interfering RNA, or siRNA, which derail the process of translating genes into proteins. They work like a dimmer switch, reducing the amount of available gene product, in this case the enzyme BACE1.

A modified lentivirus, which has been developed in Verma’s lab, delivered the siRNAs into the brain cells of the transgenic mice that were producing vast amounts of human beta-amyloid and whose brains where littered with plaques.

"When you compare the brains of treated and untreated mice, the difference is striking. Silencing BACE1 reduced the number and size of plaques by two thirds within a month, which is incredibly fast," says Singer.

Co-authors of this work also include Edward Rockenstein and Leslie Crews, both at UCSD.

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia among the elderly in the United States, affecting 4.5-5 million adults - 10 times more than those affected by Parkinson’s disease. Starting with mild memory problems and ending with severe brain damage, Alzheimer’s usually begins after the age of 60, the risk increasing with age.

Cathy Yarbrough | EurekAlert!
Further information:
http://www.salk.edu

More articles from Life Sciences:

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

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...

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

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>