Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
Demo Company
PURITAN MEDICAL

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



Channels

Genomics/Proteomics

view channel
Image: An activated PTEN dimer that contains two non-mutant proteins (A) can transform the functional lipid (D) on the cellular membrane (E) into a chemical form that tunes down cancer predilection. Dimers that contain a mutated protein (B) or PTEN monomers cannot transform the functional lipid (Photo courtesy of Carnegie Mellon University).

PTEN Requires a Stable Dimer Configuration to Effectively Suppress Tumor Growth

Molecular structural analysis has shown that the PTEN (phosphatase and tensin homolog) tumor suppressor can function effectively only when two wild-type alleles are present to form a stable dimer that... Read more

Lab Technologies

view channel
Image: The ChilliBlock modular system for precise, controlled cooling and heatingof biological samples (Photo courtesy of Asynt).

Modular Cooling/Heating System Safeguards Temperature-Sensitive Biological Samples

A new modular system designed for precise, controlled cooling and heating of biological samples in microplates, vials and Eppendorf tubes is now available for biotech, clinical, and life science laboratories.... Read more

Business

view channel

MS Drug Deal to Net More Than USD 1 Billion

A pharmaceutical company based in Switzerland has purchased the remaining rights to the multiple sclerosis drug Ofatumumab, which will allow it to continue development of the compound for treating relapsing remitting multiple sclerosis (RRMS) and similar autoimmune diseases. Novartis (Basel, Switzerland) recently announced... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.