Navigation Links
Experimental Alzheimer's disease drugs might help patients with nerve injuries
Date:4/13/2011

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 "-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 muscles or other nerve cells 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."


'/>"/>

Contact: Christen Brownlee
cbrownlee@jhmi.edu
410-955-7832
Johns Hopkins Medical Institutions
Source:Eurekalert

Related biology news :

1. French scientist wins the Journal of Experimental Biology Outstanding Paper Prize
2. Survival in a Changing World: The Journal of Experimental Biology 2009 symposium
3. 40 minority scientists receive travel fellowships to Experimental Biology 2009 in New Orleans
4. Experimental treatment halts hypoxic-ischemic brain injury in newborns
5. Experimental treatments restore partial vision to blind people
6. Experimental drug shows promise against brain, prostate cancers
7. French scientist wins the Journal of Experimental Biology Outstanding Paper Prize 2009
8. Experimental vaccine protects monkeys against chikungunya
9. Selected highlights of the research being presented at the Experimental Biology 2010 meeting
10. Experimental treatment protects monkeys from lethal Ebola virus post-exposure
11. Flemish researchers provide the first experimental evidence of dynamic allostery in protein regulation
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/2/2016)... , June 2, 2016 The Department ... has awarded the 44 million US Dollar project, for the ... Vehicle Plates including Personalization, Enrolment, and IT Infrastructure , ... in the production and implementation of Identity Management Solutions. Numerous ... however Decatur was selected for the ...
(Date:5/20/2016)... MINNEAPOLIS , May 20, 2016  VoiceIt ... technology partnership with VoicePass. By working ... user experience.  Because VoiceIt and VoicePass take slightly ... two engines increases both security and usability. ... expressed excitement about this new partnership. ...
(Date:4/28/2016)... SAN FRANCISCO and BANGALORE, India ... part of EdgeVerve Systems, a product subsidiary of Infosys (NYSE: ... service provider, today announced a global partnership that ... convenient way to use mobile banking and payment services. ... Mobility is a key innovation area for financial services, but ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... ... Researchers at the Universita Politecnica delle Marche in Ancona combed medical journal articles ... findings are the subject of a new article on the Surviving Mesothelioma website. ... blood, lung fluid or tissue of mesothelioma patients that can help point doctors to ...
(Date:6/23/2016)... , June 23, 2016   Boston Biomedical ... novel compounds designed to target cancer stemness pathways, ... been granted Orphan Drug Designation from the U.S. ... of gastric cancer, including gastroesophageal junction (GEJ) cancer. ... designed to inhibit cancer stemness pathways by targeting ...
(Date:6/23/2016)... , June 23, 2016 Houston Methodist ... the Cy-Fair Sports Association to serve as their ... agreement, Houston Methodist Willowbrook will provide sponsorship support, ... connectivity with association coaches, volunteers, athletes and families. ... the Cy-Fair Sports Association and to bring Houston ...
(Date:6/23/2016)... NEW YORK , June, 23, 2016  The ... students to envision new ways to harness living systems ... of Modern Art (MoMA) in New York ... more than 130 participating students, showcased projects at MoMA,s ... included Paola Antonelli , MoMA,s senior curator of ...
Breaking Biology Technology: