Navigation Links
New compound stops brain cell degeneration in Alzheimer's disease

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 sai d.

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.


'"/>

Source:Northwestern University


Related biology news :

1. Researchers discover chemical compounds that affect plant growth
2. Bacterial genome sheds light on synthesizing cancer-fighting compounds
3. Scientists discover the bodys marijuana-like compounds are crucial for stress-induced pain relief
4. Evolution of taste receptor may have shaped human sensitivity to toxic compounds
5. Novel compounds show promise as safer, more potent insecticides
6. Metal-containing compounds show promise as HIV weapon
7. Natural compound from pond scum shows potential activity against Alzheimers
8. Chemical compound inhibits tumor growth, size in new mouse study
9. Seaweed yields new compounds with pharmaceutical potential
10. Phenolic compounds may explain Mediterranean diet benefits
11. UC Berkeley researchers create a biologically-inspired artificial compound eye
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/23/2016)... Massachusetts , March 23, 2016 /PRNewswire/ ... im Interesse erhöhter Sicherheit Gesichts- und Stimmerkennung ... Xura, Inc. (NASDAQ: MESG ), ... bekannt, dass das Unternehmen mit SpeechPro zusammenarbeitet, ... aus der Finanzdienstleistungsbranche, wird die Möglichkeit angeboten, ...
(Date:3/21/2016)... 22, 2016 Unique technology ... for superior security   Xura, ... of secure digital communications services, today announced it is ... offer enterprise customers, particularly those in the Financial Services ... voice authentication within a mobile app, alongside, and in ...
(Date:3/15/2016)... March 15, 2016 --> ... by Transparency Market Research "Digital Door Lock Systems Market - ... - 2023," the global digital door lock systems market in ... 2014 and is forecast to grow at a CAGR of ... small and medium enterprises (MSMEs) across the world and high ...
Breaking Biology News(10 mins):
(Date:5/23/2016)... Springs, North Carolina (PRWEB) , ... May 23, ... ... process automation and building management solutions and services based in Aurora, Ohio, has ... decade of established business in the Research Triangle Park area, this new location ...
(Date:5/20/2016)... ... ... Korean researchers say Manumycin A triggers apoptosis, or natural cell death, in malignant ... Surviving Mesothelioma has just posted an article on the new study. Click here ... study on the fact the Manumycin A, a derivative of Streptomyces parvulus, is known ...
(Date:5/19/2016)... ... 19, 2016 , ... KCAS Bioanalytical and Biomarker Services, a ... Large Molecule & Biomarker Bioanalysis. , Dr. Siddiqui has more than 15 years ... preclinical and clinical safety programs. “We’ve seen significant demand for, and we are ...
(Date:5/18/2016)... -- The Biotech industry continues to face a ... are no opportunities ahead. Today, ActiveWallSt.com has on its list ... ), Seattle Genetics Inc. (NASDAQ: SGEN ), Chiasma ... OPHT ). Sign up now to receive our ... Threshold Pharmaceuticals Inc.,s shares gained 0.68%, closing ...
Breaking Biology Technology: