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

Genomics/Proteomics

view channel
Image: Differences in the structure of a small lung artery (top row) and heart cross section (lower row) of rodents without disease (far left column); with pulmonary hypertension (middle) and a diseased rodent treated with the HDL peptide (right). Note the much narrowed lung artery, and thick walls and larger chamber of the heart in the diseased animal and improvements with 4F peptide treatment (Photo courtesy of UCLA - University of California, Los Angeles).

Apolipoprotein A-1 Mimetic Peptide Reverses Pulmonary Hypertension in Rodent Models

A small peptide that mimics the activity of apolipoprotein A-1 (apo A-1), the main protein component of the high density lipoproteins (HDL), counteracted the effects of oxidized lipids and alleviated symptoms... Read more

Therapeutics

view channel
Image: Hair follicle (blue) being attacked by T cells (green) (Photo courtesy of Christiano Lab/Columbia University Medical Center).

Hair Restoration Method Clones Patients’ Cells to Grow New Hair Follicles

Researchers have developed of a new hair restoration approach that uses a patient’s cells to grow new hair follicles. In addition, the [US] Food and Drugs Administration (FDA) recently approved a new drug... Read more

Lab Technologies

view channel
Image: Leica Microsystems launches the inverted research microscope platform Leica DMi8 (Photo courtesy of Leica Microsystems).

New Inverted Microscope Designed to Readily Adapt to Changing Research Demands

A new inverted microscope for biotech and other life science laboratories was designed to readily accommodate modifications and upgrades to allow it to keep current with changing research demands and interests.... Read more

Business

view channel

Partnership Established to Decode Bowel Disease

23andMe (Mountain View, CA,USA), a personal genetics company, is collaborating with Pfizer, Inc. (New York, NY, USA), in which the companies will seek to enroll 10,000 people with inflammatory bowel disease (IBD) in a research project designed to explore the genetic factors associated with the onset, progression, severity,... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.