Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Experimental Alzheimer's disease drugs might help patients with nerve injuries

14.04.2011
Compounds helped nerve extensions re-grow faster in mouse studies

Drugs already in development to treat Alzheimer's disease may eventually be tapped for a different purpose altogether: re-growing the ends of injured nerves to relieve pain and paralysis. According to a new Johns Hopkins study, experimental compounds originally designed to combat a protein that builds up in Alzheimer's-addled brains appear to make crushed or cut nerve endings grow back significantly faster, a potential boon for those who suffer from neuropathies or traumatic injuries.

The new drugs target a protein known as "ƒÒ-Site amyloid precursor protein cleaving enzyme 1," or BACE1, which plays a key role in generating the amyloid protein plaques that are thought to gum up normal nerve signaling in the brain. Previous laboratory research showed that BACE1 also is involved in creating the insulation material known as myelin, which coats the projections that nerve cells extend to connect with each other, as well as generating a molecular cascade that causes these projections to degenerate when they're injured.

Based on these earlier findings, assistant professor of neurology Mohamed Farah, Ph.D., professor of neurology John Griffin, M.D., and their colleagues tried blocking the action of BACE1 to analyze the effect on injured axon projections. The researchers started their experiments with mice whose ability to make BACE1 had been genetically knocked out. After these animals' sciatic nerves were cut or crushed, the scientists closely watched what happened as the axons regenerated.

Compared to normal mice that make BACE1, the animals lacking this protein cleaned up the debris around the injury site significantly faster. Since this debris can inhibit regeneration, Farah and his colleagues expected that the axons would re-grow faster. Sure enough, the cut ends of the animals' nerve cells generated more new sprouts, which grew into extensions that reached their targets ¡X muscles or other nerve cells ¡X days faster than the mice that made BACE1.

Hopeful that compounds able to block BACE1 activity would have a similar effect, Farah and Griffin's team worked with two experimental drugs already developed to target Alzheimer's disease (BACE1 inhibitor IV, produced by Calbiochem, and WAY 258131, a Wyeth compound that was synthesized by researchers at Johns Hopkins Brain Science Institute for this study). Mice given either of the two drugs systemically after nerve injuries had a similar increase in re-growth, though less pronounced. This was expected, explains Farah, since the drugs dampen the effect of BACE1 without removing it entirely as in the genetic knockout mice.

The Hopkins researchers said their proof of the principle work, published in the Journal of Neuroscience on April 13, was reason to celebrate. "Anything that speeds nerve re-growth could be enormously helpful to people with nerve injuries caused by a range of injuries and diseases, from diabetic neuropathy to motorcycle accidents," says Farah.

"After an injury, the environment around nerves and their target tissue sometimes degenerates before the nerves can heal, which kills the chances that the nerve will re-grow," he explains. "If we can help nerves re-grow faster, we increase the chances that they can reach their target and become healthy again after injury."

As a next step, the researchers plan to test the experimental compounds in other animal models of nerve injury, including neuropathies and spinal cord injuries.

"BACE1 inhibitors are a major drug target for many drug companies for Alzheimer's," says Griffin. "Our work may suggest that these drugs could have great utility in a very large clinical population with tremendous unmet need. Validation of our early research in other animal models of nerve injury will set the stage for further clinical investigation."

Other Johns Hopkins researchers who participated in this study include Bao Han Pan, Ph.D., Paul N. Hoffman, M.D., Ph.D., Dana Ferraris, Ph.D., Takashi Tsukamoto, Ph.D., Thien Nguyen, M.D., Ph.D., Philip C. Wong, Ph.D., Donald L. Price, M.D., and Barbara S. Slusher, Ph.D., M.B.A.

For more information, go to:

http://neuroscience.jhu.edu/JohnGriffin.php
http://www.hopkinsmedicine.org/neurology_neurosurgery

Christen Brownlee | EurekAlert!
Further information:
http://www.jhmi.edu

Further reports about: Alzheimer' BACE1 animal models nerve cell nerve injury

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

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: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>