Better treatment for macular degeneration shows promise

Date: Sep-16-2013New research on mice raises hope of a better, more lasting treatment for macular degeneration, which uses
a class of drugs known as MDM2 inhibitors to regress the abnormal blood vessels responsible for the vision loss
associated with the disease.

Researchers at the University of North Carolina (UNC) School of Medicine and colleagues write about their findings
in a recent online issue of the Journal of Clinical Investigation.

Senior author Sai Chavala, assistant professor of Ophthalmology and Cell Biology & Physiology at the UNC School of
Medicine says:

"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."

Macular degeneration is an eye disease that leads to loss of central vision. It is the major cause of vision loss
among older people in the US, where around 11 million Americans have some form of macular degeneration.

A new treatment for macular degeneration, an eye disease that affects 11 million Americans, is able to target leaky blood vessels directly, researchers say.

Macular degeneration destroys the macula, the part of the eye that provides sharp, central vision. People with the
disease find it increasingly difficult to do normal daily things, like drive, read and watch TV.

When macular degeneration occurs over the age of 50, it is called age-related macular degeneration (AMD).

AMD always starts as a "dry" form, which can cause blurred vision or blind spots. But around 1 in 5 people with AMD
go on to develop the "wet" form, where abnormal blood vessels grow in the eye and start leaking fluid or blood,
causing loss of vision.

The best treatment that is currently available uses an antibody, anti-VEGF, that is injected into the eye. But the
injection has to be given every 4 or 8 weeks, depending on the brand, which makes it expensive and time-consuming, plus it exposes the patient to risk of infection.

In June 2011, a US Food and Drug Administration (FDA) panel approved an anti-VEGF treatment of wet AMD that only has to be
injected every 8 weeks.

However, the hope following the promising results of this new study on mice is that patients will have a long-lasting
treatment so they will not need so many injections.

Prof. Chavala, who is also director of UNC School of Medicine's Laboratory for Retinal Rehabilitation, and who practises
at the Kittner Eye Center at UNC Health Care, says such a treatment would reduce patients' "overall risk of eye
infections, and also potentially lower the economic burden of this condition by reducing treatment costs."

The advantage that MDM2 inhibitors have over anti-VEGF is that they target the leaky blood vessels directly, whereas
anti-VEGF targets the growth factors that lead to abnormal blood vessels. It is the ability to target the vessels
directly that potentially offers a lasting effect, say the researchers.

For their study, the team looked at the effect of the MDM2 inhibitors in cell cultures and in mice with macular
degeneration.

They found the drug activates a protein called p53, a master regulator protein that decides whether a cell lives or
dies.

Prof. Chavala says:

"By activating p53, we can initiate the cell death process in these abnormal blood vessels."

MDM2 inhibitors may also offer advantages over another treatment currently being trialled for wet AMD: low-dose radiation.

The low-dose radiation treatment also triggers p53, by causing damage to cells' DNA. But MDM2
inhibitors activate p53 without causing DNA damage.

Also, MDM2 inhibitors can be given by eye injection, whereas some forms of radiation treatment can only be done with
surgery.

Prof. Chaval is the founder of a company that plans to commercialize new treatments for eye diseases. The company has also filed
a patent for using MDM2 inhibitors to treat them.

In 2010, researchers reported that omega-3-rich foods
protect seniors from AMD.

Written by Catharine Paddock PhD

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