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 New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

NASA Protects its super heroes from space weather

17.08.2017 | Physics and Astronomy

Spray-on electric rainbows: Making safer electrochromic inks

17.08.2017 | Materials Sciences

Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

17.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>