Features | Partner Sites | Information | LinkXpress
Sign In
PZ HTL SA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Nutlin-3 Shows Promise for Treating Macular Degeneration

By BiotechDaily International staff writers
Posted on 23 Sep 2013
Image: Subretinal hemorrhage in a wet macular degeneration patient (Photo courtesy of Chavala Laboratory, University of North Carolina).
Image: Subretinal hemorrhage in a wet macular degeneration patient (Photo courtesy of Chavala Laboratory, University of North Carolina).
Image: Normal adult mouse retinal vasculature (Photo courtesy of Chavala Laboratory, University of North Carolina).
Image: Normal adult mouse retinal vasculature (Photo courtesy of Chavala Laboratory, University of North Carolina).
A low molecular weight drug, Nutlin-3, prevented growth of new blood vessels in cell cultures and in a mouse model and may prove to be the treatment of choice for macular degeneration.

Age-related macular degeneration characterized by development of abnormal blood vessels in the eye is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as monoclonal antibodies that target vascular endothelial growth factor) are effective in treating the syndrome, but have not led to a durable effect and often require indefinite treatment.

Investigators at the University of North Carolina (Chapel Hill, USA) have been working with the drug Nutlin-3. Nutlins are cis-imidazoline analogs that inhibit the interaction between the enzyme MDM2 and the tumor suppressor p53. MDM2 is an E3 ubiquitin-protein ligase. It binds to p53 and targets it to ubiquitin-mediated degradation in proteasomes. Nutlin-3 has been shown to affect the production of p53 within minutes.

A paper published in the September 9, 2013, online edition of the Journal of Clinical Investigation revealed that a functional p53 pathway was essential for the Nutlin-3-mediated inhibition of new blood vessel formation in the retina. Disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3.

Nutlin-3 did not inhibit established, mature blood vessels in the adult mouse retina, suggesting that only proliferating retinal vessels are sensitive to Nutlin-3. Furthermore, Nutlin-3 inhibited angiogenesis in nonretinal models such as the hind limb ischemia model.

Nutlin-3 eliminated the newly forming, problematic blood vessels associated with wet macular degeneration by activating the p53 protein, a master regulator that determines whether a cell lives or dies. “By activating p53, we can initiate the cell death process in these abnormal blood vessels,” said senior author Dr. Sai Chavala, assistant professor of ophthalmology and cell biology and physiology at the University of North Carolina. “We believe we may have found an optimized treatment for macular degeneration. Our hope is that MDM2 inhibitors would reduce the treatment burden on both patients and physicians.”

Related Links:
University of North Carolina School of Medicine



BIOSIGMA S.R.L.
RANDOX LABORATORIES
SLAS - Society for Laboratory Automation and Screening
comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: A 3-dimensional picture reveals how the antibodies in the experimental drug Zmapp bind to Ebola virus (Photo courtesy of the Scripps Research Institute).

Electron Microscope Imaging Shows How Experimental Anti-Ebola Drug Works

Electron microscope imaging has revealed how the experimental drug ZMapp binds to the Ebolavirus and provides insights into how the drug prevents growth of the pathogen. ZMapp, which was developed by... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Lab Technologies

view channel

e-Incubator Technology Provides Real-Time Imaging of Bioengineered Tissues in a Controlled Unit

A new e-incubator, an innovative miniature incubator that is compatible with magnetic resonance imaging (MRI), enables scientists to grow tissue-engineered constructs under a controlled setting and to study their growth and development in real time without risk of contamination or damage. Offering the potential to test... Read more

Business

view channel

Two Industry Partnerships Initiated to Fuel Neuroscience Research

Faster, more complex neural research is now attainable by combining technology from two research companies. Blackrock Microsystems, LLC (Salt Lake City, UT, USA), a developer of neuroscience research equipment, announced partnerships with two neuroscience research firms—PhenoSys, GmbH (Berlin, Germany) and NAN Instruments, Ltd.... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.