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January/February 2008 Issue

• Remedying Chronic Dry Eye, An Interview with: Robert Latkany, M.D.
• Digi Sbarro Institute Lab Project Opens on Second Life
• Speeding Up Drug Development

Remedying Chronic Dry Eye
An Interview with:
Robert Latkany, M.D.

Pierpaolo Basso
Editor
15 Jan/Feb 2008

Chronic Dry Eye, a group of disorders affecting the film of tears that coat the eye, is on the rise. The condition, which can cause burning, irritation, inflammation and a ‘gritty’ sensation in the eye, currently affects about 10 to 14 million Americans, many of them older women.

But the good news is that symptoms of dry eye are treatable. To gain a better understanding of the condition and how to deal with it, we interviewed Robert Latkany, M.D., the founder and director of the Dry Eye Clinic at the New York Eye & Ear Infirmary and author of:

The Dry Eye Remedy:
The Complete Guide to Restoring the Health and Beauty of Your Eyes

Why did you write the book?

I wrote the book because most people do not realize the seriousness of this disease and I wanted to reach out to a larger audience to get this message across. There is help around the corner.

How do computers and television contribute to chronic dry eye?

The problem with personal computers or television is that we tend to stare at them and forget to blink. Not blinking enough will lead to dry eyes. We need to blink to spread the tear film over our eyes to keep them moist and protect them from drying out. Regular computer and TV will dry out our eyes.

What is the top causes of chronic dry eye?

The top causes include inflammation from a variety of causes and hormonal changes. Some specific causes include rosacea, surgery like LASIK and blepharoplasty, autoimmune conditions like Sjogren's syndrome and diabetes, lagophthalmos, contact lenses, and menopause.

How does aging impact the tear film of the eyes?

As we age our androgen levels drop. There has been a direct link to drop in androgens and dry eyes. There is so much more that we do not know, but will soon find out about the hormonal influence on dry eyes.

Dysfunction of the meibomian glands, a special kind of sebaceous glands at the rim of the eyelids, also increases as we age. This produces a poorer quality of tear film over the eye.

Another cause of chronic dry eye that you mention is LASIK or laser surgery therapy. According to your book, LASIK can sever more than 70% (percent) of the superficial corneal nerves. Can this procedure contribute to long time eye damage?

LASIK rarely promotes chronic long-term dry eye damage. A more likely scenario is that if you have an untreated dry eye condition to begin with, your eyes will worsen after corrective vision surgery and you won’t be happy with the results. My advice is to care for your dry eyes first and then see if LASIK is for you.

How does diet aid chronic dry eyes?

An increased intake of omega 3 essential fatty acids reduce the likelihood of dry eye syndrome. Great sources of omega 3 essential fatty acids include fish oil, flax seeds, walnuts, canola oil, and soy oil. Everyone, not just dry eye sufferers, should have more omega-3 fatty acids as it has many proven benefits.

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January/February 2008 Issue

Digi Sbarro Institute Lab Project Opens on Second Life

Ilene Raymond
Editor-in-Chief
15 Jan/Feb 2008

The Sbarro Health Research Organization www.shro.org, a nonprofit research group, has opened its Internet headquarters on Second Life, the parallel internet-based virtual world created in 2003 by Linden Research.

The Dig S Lab project team created the Sbarro compound on the futuristic Second Life with the aim of providing a dynamic space for open discussion, learning, and scientific interaction and collaboration. The island includes reproductions of real life laboratories, international conference rooms and innovative structures.

Digi S Lab is one of the first Virtual Lab projects in the world. It will showcase the daily efforts of young and expert scientists and doctors to develop innovative techniques in genetics, molecular biology and medicine.

The Sbarro Institute for Cancer Research and Molecular Medicine in Philadelphia was established in 1993. “We hope to use this multi-scientific environment as a place where we might eventually develop new scientific devices,” says Antonio Giordano, M.D., Ph.D., the President and Founder of the SHRO. “The virtual research laboratories may be the beginning of a new path, which will lead us to improve our research results and help to aggregate the best minds in the field.”

“With the assistance of WorldWired, Inc. Informatics Company we have created a unique space which is impressively dynamic and real", says Giuseppe Russo, Ph.D., the SHRO Chief Executive Officer of the project, We spent a lot of energy in creating a unique lab space focusing our attention to enhance the teaching of Biotechnology, Bioinformatics and Molecular Medicine.”

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January/February 2008 Issue

Speeding Up Drug Development

Ilene Raymond
Editor-in-Chief
15 Jan/Feb 2008

Guidance from an innovative computational approach could speed up the process and cut down the cost of new drug development, researchers from the University of Chicago Medical Center and Columbia University suggest in a study to be published in the February 2008 issue of Genome Research, available early online.

The researchers analyzed specific properties of the human genes and proteins that serve as targets for nearly a thousand FDA-approved drugs. They identified a number of characteristics that were common among successful drug targets–and especially common among high-revenue drugs.

"To make a good drug, you need to find a good drug target," said Andrey Rzhetsky, PhD, professor of medicine at the University of Chicago and senior author of the study. "Here we provide guidelines for more efficient target screening. When a drug company must decide which target to pursue among pathologic pathways, this could provide useful estimates of each target's expected success rate."

Gleevec, Prozac, Viagra: these successful drugs all target specific proteins and provoke a desired response. They reward the people who need them, as well as to those who invent, manufacture and market them.

But the development of a new drug is complicated and expensive, "a fusion of art and science," the authors note. It involves finding an accessible drug target and a molecule that binds that target as selectively as possible. Then it must trigger a desirable physiological change.

But "every highly visible success," the authors note, "rests on an iceberg of invisible failures." Since the estimated cost of developing a new drug ranges from $800 million to $1.2 billion, "information that helps only a little bit," Rzhetsky said, "can still be quite valuable."

What characteristics, they asked, distinguished the targets that eventually became the focus of such successful drugs? How are these genes or proteins different from the tens of thousands of less desirable targets?

To find out, the researchers looked at the relationships between 919 successful drugs, their human gene or protein targets, and the functional properties of those targets.

They found that most successful drugs are very precise; 62% of them have only one specific target.

But that's just a start. "A target molecule with an appropriate, 'drugable' structure is a necessary but not sufficient condition for success," write the authors. But the selection of a prospective drug target is "a complicated balance of many considerations,"

Additional properties that distinguish most good targets include:

• Connectivity: how many other proteins does the target protein interact with directly? Effective drugs targets--according to Rzhetsky and colleague Lixia Yao, from Columbia University--interact with about nine other genes or proteins, which is above average but not extremely high. This is enough connections to have a significant impact but not so many as to multiply the risks of serious side effects. The very-high-revenue drugs, the authors note, tend to target genes and proteins with slightly lower connectivity.

• Betweeness: how often does this protein serve as the shortest path between two networks of proteins? Successful drugs, they found, tend to bridge two of more clusters of interacting molecules.

• Consistency: how much does the gene for this protein vary from person to person? Limited individual variation is better, so the drug works the same way in most people.

• Tissue specificity: Where is the gene for the drug target expressed? In just one tissue, say brain, or skin, or all over the body? Ideally, the researchers found that the best targets were genes or proteins primarily expressed in one specific tissue, so the drug treats the disease at its core, without interfering with other, healthy tissues or organs, and thus causes fewer side-effects. Six tissue types, they found, were significantly "undertargeted" by pharmaceutical research: male reproductive tissues, embryonic structures, skin, cartilage, bone and lymph.

•Overlap: Finally, successful drug targets significantly overlap with disease genes--those in which a mutation can cause a specific disease, such as cystic fibrosis--and with essential genes, that are required for normal development.

"We found that genes associated with successful FDA-approved drugs have several properties at the network, sequence, and tissue-expression levels that significantly distinguish them from other human genes,"the authors conclude. "Although the drug target-selection guidelines that we suggest cannot replace expensive experiments, they can help at the earliest stage of a drug-development project."

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