Features | Partner Sites | Information | LinkXpress
Sign In
JIB
GLOBETECH PUBLISHING
GLOBETECH PUBLISHING

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



comments powered by Disqus

Channels

Therapeutics

view channel
Image: This type of electronic pacemaker could become obsolete if induction of biological pacemaker cells by gene therapy proves successful (Photo courtesy of Wikimedia Commons).

Gene Therapy Induces Functional Pacemaker Cells in Pig Heart Failure Model

Cardiovascular disease researchers working with a porcine heart failure model have demonstrated the practicality of using gene therapy to replace implanted electronic pacemakers to regulate heartbeat.... Read more

Lab Technologies

view channel
Image: The DrySyn MULTI converts any standard hotplate stirrer into a high performance reaction block (Photo courtesy of Asynt).

New Reaction Vessel Heating System Is Cleaner and Safer

Biotech and other life science researchers can create a safer, cleaner, and more efficient working environment in their laboratories by switching from oil bath-based heating of reaction vessels to a new... Read more

Business

view channel

Global Computational Biology Sector Expected to Reach over USD 4 Billion by 2020

The global market for computational biology is expected to reach USD 4.285 billion by 2020 growing at a compound annual growth rate (CAGR) of 21.1%, according to new market research. Steady surge in the usage and application of computational biology for bioinformatics R&D programs designed for sequencing genomes... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.