Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New strategy may protect brain against stroke, Parkinson’s and Alzheimer’s

22.10.2002


Researchers at the National Institutes of Health have developed several drug candidates that show promise in animal studies in protecting the brain against sudden damage from stroke, with the potential for fighting chronic neurodegenerative conditions like Parkinson’s and Alzheimer’s disease. The drugs, called p53 inhibitors, attack a key protein involved in nerve cell death and represent a new strategy for preserving brain function following sudden injury or chronic disease, according to the researchers.



Their findings will appear in the Nov. 7 print issue of the Journal of Medicinal Chemistry, a peer-reviewed publication of the American Chemical Society, the world’s largest scientific society.

"This is a completely new therapeutic strategy for Alzheimer’s and other neurodegenerative diseases, which warrants further assessment to allow it to move to clinical trials," says Nigel H. Greig, Ph.D., a researcher with the National Institute on Aging’s Intramural Research Program in Baltimore, Md., and chief investigator for the study. "If it works, it could provide a new treatment approach for a wide range of neurological diseases."


The research is limited to cell and animal studies for now, but if all goes well, human clinical trials could begin in two to three years, Greig says. The new drugs could provide relief for millions of Americans who suffer from mental and physical decline due to neurological damage and offer hope to those who are at increased risk due to advancing age.

Drugs currently used to treat neurological disease and injuries provide temporary relief of symptoms but do not stop or slow the underlying neurodegenerative process. The new experimental drugs, by contrast, target the common, underlying cause of this destructive process: the death of brain cells.

"By turning off cell death, you rescue brain cells from lethal insult," Greig says. He compares other drugs to "bandages" that help alleviate brain damage after it occurs, whereas p53 inhibitors act as "seat belts" that help prevent damage from occurring in the first place.

The main target of these drugs, p53, is a common protein found in cells that triggers the biochemical cascade of events leading to cell death. As cells die, new, healthy ones normally replace them. But in the diseased or injured brain, cell death can cause devastating damage, as brain cells cannot regenerate. The researchers theorized that by inactivating the protein temporarily, further brain damage might be prevented.

The researchers identified one compound, called pifithrin-alpha (PFT), which was shown in previous studies to inhibit p53. They then designed, synthesized and tested analogues of this compound to see whether they would work against cultured brain cells and animal models of neurodegenerative disease.

In laboratory tests, brain cells exposed to a series of toxic chemicals survived longer when given the inhibitor compound. In subsequent tests using a rodent model of stroke, the severity of stroke damage was significantly decreased in animals that received the inhibitor compounds compared to those that did not receive it, the researchers found.

Evidence for the drugs’ potential effectiveness against chronic neurodegenerative diseases is growing. In a related study, the researchers found that the drugs appear to prevent nerve damage in a mouse model of Parkinson’s disease.

In another study, the researchers showed that the compounds protect brain cells against beta amyloid, a toxic protein associated with Alzheimer’s disease. They are now planning to test the experimental drugs in animal models of the disease.

The new drugs will probably first be used to treat stroke, brain injury (from sports and motor vehicle accidents) or other conditions characterized by sudden brain trauma, the researchers say. If the compounds prove safe, they could later be extended to long-term diseases like Alzheimer’s, Parkinson’s, and Lou Gehrig’s (amyotrophic lateral sclerosis, or ALS).

The researchers caution that they need to first make sure that the inhibitors don’t cause side effects in other cells of the body. Other studies show that mice that have no p53 have an increased incidence of cancer, while those that have high levels of p53 experience premature aging.

"You have to have just the right balance," Greig says. Ideally, the compounds will work only temporarily and will then be broken down by the body.

Greig and his associates are currently testing various drug analogues to see which ones work the best. Once developed, the drugs can either be used as an oral pill or intravenously, depending on how quickly they need to be administered.

The National Institute on Aging provided funding for this study.

Dr. Greig’s associates in this study were Xiaoxiang Zhu, Ph.D., Qian-sheng Yu, Ph.D., Roy G. Cutler, M.S., Carsten W. Culmsee, Ph.D., Harold W. Holloway, B.S., Mark P. Mattson, Ph.D., all of the NIA’s Intramural Research Program; and Debomoy K. Lahiri, Ph.D., of Indiana University School of Medicine in Indianapolis, Ind.


The online version of the research paper cited above was initially published Oct. 3 on the journal’s Web site. Journalists can arrange access to this site by sending an e-mail to newsroom@acs.org or calling the contact person for this release.

Nigel H. Greig, Ph.D., is chief of the Drug Design & Development Section in the Laboratory of Neurosciences at the National Institute on Aging’s Intramural Research Program in Baltimore, Md.

Beverly Hassell | EurekAlert!
Further information:
http://www.acs.org/

More articles from Health and Medicine:

nachricht Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Foods of the future
15.08.2018 | Georg-August-Universität Göttingen

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: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Quantum bugs, meet your new swatter

20.08.2018 | Information Technology

A novel synthetic antibody enables conditional “protein knockdown” in vertebrates

20.08.2018 | Life Sciences

Metamolds: Molding a mold

20.08.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>