Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New compound stops brain cell degeneration in Alzheimer’s disease

23.01.2006


Drug discovery researchers at Northwestern University have developed a novel orally administered compound specifically targeted to suppress brain cell inflammation and neuron loss associated with Alzheimer’s disease.



The compound is also rapidly absorbed by the brain and is non-toxic – important considerations for a central nervous system drug that might need to be taken for extended periods.

As described in the Jan. 11 issue of the Journal of Neuroscience, the compound, called MW01-5-188WH, selectively inhibits production of pro-inflammatory proteins called cytokines by glia, important cells of the central nervous system that normally help the body mount a response, but are overactivated in certain neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, stroke and traumatic brain injury.


The compound was designed and synthesized in the laboratory of D. Martin Watterson at Northwestern University Feinberg School of Medicine, using a synthetic chemistry platform developed in his lab by researchers at the Northwestern University Center for Drug Discovery and Chemical Biology (CDDCB) for the rapid discovery of new potential therapeutic compounds.

Watterson is co-director of the CDDCB, the J.G. Searle Professor of Molecular Biology and Biochemistry and professor of molecular pharmacology and biological chemistry at the Feinberg School.

The efficacy and safety of the compound in an animal model of Alzheimer’s disease was evaluated in collaboration with Linda J. Van Eldik, co-director of the CDDCB and professor of cell and molecular biology at Feinberg.

Besides providing a lead compound for drug development, the study has important implications for drug discovery in neurodegenerative diseases in general because it provides proof of concept that targeting over-production of cytokines by activated glia is a viable approach that has the potential to modulate disease onset and progression, the researchers said.

Decline of cognitive functions linked to the part of the brain called the hippocampus is a clinical hallmark of Alzheimer’s disease. The report demonstrates that targeting excessive glial activation can suppress brain inflammation and neuron dysfunction in the hippocampus and protect against cognitive decline in an animal model.

Neuron dysfunction can lead to further glia activation and contribute to further exacerbation of the disease process. The Northwestern researchers found that 188WH and related compounds slowed or reversed the progression of the neuroinflammatory cascade and reduced human amyloid beta-induced glia activation in a mouse specially designed to develop many of the signs of Alzheimer’s disease, including neuroinflammation, neuronal and synaptic degeneration and behavioral deficits.

The compound also restored normal levels of markers of synaptic dysfunction in the hippocampus, the area of the brain that helps regulate memory and is gradually destroyed in neurodegenerative diseases such as Alzheimer’s. Treatment with the compound also attenuated Alzheimer’s-like behavioral deficits in the mice that are due to injury to the hippocampus.

While previous research by the authors and many other investigators in the field has linked plaques, tangles and neuronal injury to synaptic dysfunction and cognitive decline, the direct linkage of glia to these processes and their potential as a selective target for new therapies has not previously been implicated so directly.

There are three key aspects of the report, Watterson said.

"First, a novel compound for development into a new class of Alzheimer’s disease therapeutics that target disease has been described. Second, an innovative approach was used for the rapid and cost-effective discovery of orally bioavailable, safe and efficacious compounds, and this approach can be extended to other disease areas," Watterson said.

"Third, the design, synthesis and in vivo analyses were carried out by a new generation of young scientists trained in our educational program to instruct the next generation of interdisciplinary scientists," Watterson said.

Northwestern University patented the compound designated 188WH and has exclusively licensed the patent rights to NeuroMedix, Inc., for clinical development.

Elizabeth Crown | EurekAlert!
Further information:
http://www.northwestern.edu

More articles from Life Sciences:

nachricht Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society

nachricht New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

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

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>