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
Christen Brownlee | EurekAlert!
Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research