Exploiting Cortistatins' Essence

Simple analogs of a complex natural product may protect against loss of vision
Carmen Drahl

By making simplified versions of cortistatins, marine natural products that halt new blood vessel growth, researchers can treat excessive vessel growth in mice with macular degeneration. The analogs may inspire a new class of medications for the disease, which is a leading cause of vision loss.

Cortistatins A and J are potent blockers of angiogenesis, or new blood vessel growth, but the natural supply is scarce and chemical syntheses of the cortistatins haven't produced enough material for animal testing. Chemists Barbara Czakó, László Kürti, and E. J. Corey at Harvard University decided to study analogs instead.

"What distinguishes cortistatins are two basic groups at opposite ends of a steroidlike scaffold that are important for bioactivity," Corey says. His team incorporated those essential groups, a dimethylamino and an isoquinoline group, on opposite ends of an easy-to-build steroid and made refinements to optimize anti-angiogenic activity in cells. In collaboration with vascular biologists Akiko Mammoto and Donald E. Ingber of Harvard Medical School, they found that some of their compounds blocked angiogenesis in a mouse model of macular degeneration but did not show signs of toxicity in cellular assays (J. Am. Chem. Soc., DOI: 10.1021/ja902601e).

The most effective pharmaceutical treatment for macular degeneration is administered by injection into the eye, Corey notes. All of his team’s most potent analogs are water soluble and could lead to an eye-drop-based treatment, he says.

Chemist Samuel J. Danishefsky of Memorial Sloan-Kettering Cancer Center and Columbia University praised the work, saying that Corey's team “has increased the scope of the cortistatins by weaving them into a steroid setting which provided a doable terrain for chemical synthesis.”

"In terms of an exercise in blending intuition and rational discovery, this paper could emerge as a classic," Danishefsky adds.

Studies from other groups suggest that inhibitors of the particular angiogenesis pathway that the cortistatin analogs target may lead to side effects, cautions David A. Cheresh, who studies tumor angiogenesis at the University of California, San Diego. Nonetheless, the analogs "represent exciting new leads in the search for the next class of anti-angiogenic agents" and should be studied further, he adds.

Corey tells C&EN that the cortistatin analogs are effective in mice at very low doses of less than 1 mg and would also be locally administered. Therefore, the amount of drug that the rest of the body would see is likely to be essentially zero, vastly reducing the potential for side effects, he says.

In related work, independent teams led by Hiromasa Kiyota at Tohoku University in Japan and Phil S. Baran at Scripps Research Institute have tested simplified cortistatins in cells, but neither team has reported animal studies (Biosci. Biotechnol. Biochem. 2008, 72, 2992; Angew. Chem. Int. Ed., DOI: 10.1002/anie.200901116).

First Bionic Eye to Undergo Clinical Tests by 2011

The first clinical tests of a bionic eye are likely within two years and commercialization within five, according to researchers.

A bionic eye is a form of neural prosthesis intended to partially restore lost vision or amplify existing vision.

There is a lot of promising research being done right now. We are living in a very exciting time.

However, we can't put our plans and dreams on hold until this research delivers a cure.

I will never forget the day that I discovered a Telesensory video magnifier in a university library. It was 1977. I was just about to drop out of college before I made this discovery.

That video magnifier made it possible for me to complete college and live my dream as a public school teacher for 21 years!

Today I am very proud to own Amazing Video Magnifiers where I distribute only Telesensory video magnifiers.

They are, in my opinion, the most reliable and cost efficient.

I encourage you to visit the site and read about the various outstanding units.

New Medical Study Establishes First-Ever Long-Term Benefits for Macular Degeneration Sufferers Using Macular Health Vitamin Supplement

New Medical Study Establishes First-Ever Long-Term Benefits for Macular Degeneration Sufferers Using Macular Health Vitamin Supplement

Eye disease product has the potential to preserve vision for millions

BIRMINGHAM, Ala., April 28 /PRNewswire/ -- As many as 17.8 million people will suffer from age-related macular degeneration (AMD) by 2050 and 1.57 million will be blind from the disease, according to the U.S. Centers for Disease Control and Prevention. However, a new medical study by a group of retina specialists at the Callahan Eye Foundation Hospital at the University of Alabama Birmingham (UAB) indicates that with the use of the Macular Health vitamin supplement there is a way to reduce these numbers and potentially preserve the vision of millions.

The second phase of the Multifocal Electroretinogram (MERG) study recently revealed that patients suffering from AMD experienced long-term benefits from taking Macular Health, a special combination of supplemental vitamins, minerals and carotenoids. Phase I of the MERG study, completed in 2005, confirmed an average of 16 percent improvement in vision after taking Macular Health for only 12 weeks. Phase II measured the vision function of the same patients two years later and found an average improvement in vision of 17 percent.

"The outcome of this study is extremely encouraging for sufferers of age-related macular degeneration," says John O. Mason, III, MD, researcher and retinal specialist at the Callahan Eye Foundation Hospital. "These new findings prove that Macular Health can slow vision loss and actually improve vision function over time."

MERG testing was used to gauge the vision of AMD patients before and after using the Macular Health supplement. The test results of patients taking Macular Health were compared to results of a control group that did not take the supplement. Phase II of the study was accepted by the Association for Research and Vision in Ophthalmology (ARVO) for poster presentation. Mason and a team of retina specialists will continue to monitor study participants to evaluate improvement in eye health and vision with the use of Macular Health.

Jeffery McAnnally, President of Macular Health, LLC, says, "On behalf of the Macular Health Company, I am pleased to share this additional proof of Macular Health's effectiveness. Not only is Macular Health the most affordable product of its kind on the market today, it is the easiest to take."

An estimated 9 million people currently suffer from AMD, and one-third of adults over 70 are afflicted with this incurable disease. AMD is the leading cause of blindness in Americans 50 years of age and older. AMD is a breakdown of the macula of the eye that typically occurs during the aging process. Damage of the macula increases the difficulty of seeing fine details and even faces clearly.

To learn more about age-related macular degeneration or the Macular Health vitamin supplement, visit www.macularhealth.com. To speak with John O. Mason, III, MD, please contact Julie Ward at 205.503.5955 or julie@styleadvertising.com.
Website: http://www.macularhealth.com/

Possible Cure on Horizon

It's a sight for sore eyes.

Stem cell therapy to cure blindness is being developed by British scientists, and surgeons believe it could become a simple procedure that will be available in six or seven years' time, the London Times reported.

The process involves replacing a layer of dying cells with fresh ones created from embryonic stem cells.

It targets age-related macular degeneration (AMD), one of the most common causes of blindness, which involves the loss of eye cells.

"This is a huge step forward for patients," Tom Bremridge, chief executive of the Macular Disease Society, told the Times. "We are extremely pleased that the big guns have become involved, because, once this treatment is validated, it will be made available to a huge volume of patients."

Embryonic stem cells have the ability to develop into all types of body tissue.

Their use is controversial, however, because it involves the destruction of human embryos.

Lab tests done by the British team have shown that stem cells can prevent blindness in rats, and similar elements work on pigs.

A clinical trial is expected within two years.

It will most likely be the second in the world to use embryonic stem cells on humans. The first, spinal cord injury sufferers, will start later this year in the United States.

Sirion gets FDA Fast Track designation for sight-preserving drug

Sirion gets FDA Fast Track designation for sight-preserving drug
Tampa Bay Business Journal

Sirion Therapeutics Inc. announced positive results from a clinical trial evaluating a treatment for certain persons with macular degeneration.

The Phase II trial evaluated fenretinide as a treatment for geographic atrophy associated with age-related macular degeneration.

Sirion describes fenretinide as an oral vitamin A binding protein antagonist. Geographic atrophy is the most advanced form of dry age-related macular degeneration.

An analysis of the Phase II data showed slower growth of lesions in patients treated with oral fenretinide than in patients who received a placebo, a release from Sirion said.

Sirion will continue the Phase II study and will meet with scientific advisers and the Food and Drug Administration to design a Phase III study, the release said.

The effort by Sirion to develop fenretinide as a treatment got an additional boost when the FDA granted it Fast Track designation, the release said. Fast Track programs of the FDA are designated to facilitate the development of drugs that are intended to treat serious or life threatening conditions and that demonstrate the potential to address an unmet medical need for such a condition.

Sirion is a privately held biopharmaceutical company based in Tampa focused on discovery, development and commercialization of products to protect and preserve eyesight.

New Drug May Help Treat, Reverse Advanced Macular Degeneration
Apr 13, 2009
Reporter: CBS News
Email Address: news@kbtx.com

As the baby boomers age and live longer, a severe sight problem called Macular Degeneration is becoming more common.
But, there are new treatments to help the condition that can lead to blindness.
Sylvia Moore was diagnosed with macular degeneration three years ago.
"If I look straight ahead at somebody's face, I don't see them at all, you'd see a blank spot, a black spot," says Moore of the disease.
Macular Degeneration is most common in seniors.
It happens when blood vessels in the back of the eye start leaking and is the leading cause of blindness in people over 65.
The good news is doctors now have more weapons than ever to fight the condition, and in some cases even reverse it.
When it's caught early, vitamin therapy can slow down the progression of macular degeneration, and in some cases laser surgery can halt vision loss.
But the latest treatment is a drug that's injected directly into the eye.
The medication targets the abnormal blood vessels leading to its shutdown and hopefully to the improvement in vision.
Moore has been getting the injections for three months and is already seeing a difference.
"Its scary when you see a needle coming at you but it doesn't hurt.... I'd rather have that than blindness," Moore says.
A new study predicts some 9 million americans will be diagnosed with macular degeneration next year.
That number is expected to double in the next 40 years.

Eye 'compensates for blind spot'

Eye 'compensates for blind spot'
Eye Peripheral vision is retained

Partially sighted and registered blind people can be taught to read and see faces again using the undamaged parts of their eyes, say experts.

When only the central vision is lost, as with the leading cause of blindness, age-related macular degeneration, peripheral vision remains intact.

And patients can be taught to exploit this, the Macular Disease Society says.

It has developed a training scheme and is calling for professionals to adopt the system across the UK.

The macula is a small area of the retina at the back of the eye made up of specialist cells which process central vision as well as the fine detail of what we see.

Our scheme has transformed lives - helping people to relearn basic skills they thought to have lost for good
Tom Bremridge
Macular Disease Society

People with macular degeneration rarely go totally blind but even those with a relatively mild version of the disease cannot drive and have difficulty reading, recognising faces and watching television.

But studies show people can be taught to use their peripheral vision to fill in the gaps, using "eccentric viewing" and "steady eye techniques".

When someone with central vision loss looks directly at an object it may disappear, go faint, blur or distort. But when they look above, below or to one side of it, they see it more clearly.

Blind spots

Eccentric viewing helps people find exactly where to focus their gaze to make their vision better.

Once this position is identified, they can be taught how to read again using the steady eye technique.

Instead of moving the eyes from left to right to read a sentence, the person should keep their eyes completely still and move the text to the left so that each word in turn moves into the area of best vision.

All UK patients with central vision loss should have the opportunity to try eccentric viewing
Mr Winfried Amoaku
Royal College of Ophthalmologists

Macular Disease Society chief executive Tom Bremridge said: "Eccentric viewing works by making the most of vision that remains.

"Our scheme has transformed lives - helping people to relearn basic skills they thought to have lost for good.

"We have 86 volunteer trainers, all with central vision loss themselves, who have trained more than 310 people in their own communities, and our waiting list of nearly 1,200 people grows every day.

"We are keen that other service providers - social services, private practitioners and primary care trusts - now take up the baton."

Mr Winfried Amoaku, of the Royal College of Ophthalmologists, said eccentric viewing could help some patients with central vision loss "cope with everyday tasks such as identifying coins while out shopping, watching television and reading".

"The trouble is, we don't know who will benefit until they have tried the training.

"All UK patients with central vision loss should have the opportunity to try eccentric viewing techniques to see if they can benefit," he said.

Marek Karas, of the Royal National Institute of Blind People, also supported the research advances.

"Although there is still ongoing discussion among experts over the best form of training for this type of therapy, we welcome with interest these latest developments."

Between 25 and 30 million people worldwide have macular degeneration. But as the population ages, this figure will rise.

It is estimated that the number of people affected will triple by 2025.