'Orphan' sleep drug may be potent cancer-fighting agent

And because of the FDA, this drug will never become generally available.  It takes half a billion dollars to get a drug through the FDA and since the drug will not be patentable, nobody is going to spend that sort of money on it

An inexpensive "orphan drug" used to treat sleep disorders appears to be a potent inhibitor of cancer cells, according to a new study led by scientists at Fred Hutchinson Cancer Research Center.

Their novel approach, using groundbreaking technology that allows rapid analysis of the genome, has broad implications for the development of safer, more-effective cancer therapies. The findings are published in the May 21 issue of the Proceedings of the National Academy of Sciences.

A research team led by corresponding author Carla Grandori, M.D., Ph.D., an investigator in the Hutchinson Center's Human Biology Division, used a high-speed robotic technology called high-throughput screening and a powerful genetic technique called siRNA gene silencing to uncover fatal weaknesses in cancer cells driven by an oncogene known as "Myc," which is hyperactive in many cancers, including those of the brain, breast, lung, ovary and liver.

Myc traditionally has been considered an "undruggable" oncogene because it is not readily neutralized by the kind of small, stable molecule that would work as a cancer drug. Even if such drugs existed, they would likely disable Myc in normal cells as well, which would create toxic side effects.

"Fortunately, Myc-driven cancer cells have an Achilles heel," Grandori said. "Their rapid growth and division damages their DNA, and they rely on other genes to repair that damage. Disabling those genes can cripple the cancer's ability to grow."

Grandori and colleagues found more than 100 genes which, when blocked, caused the death of Myc-driven cancer cells but not normal cells. This suggests that each of these genes is a potential target for a new, nontoxic cancer therapy.

One of these genes, CSNK 1 epsilon, is especially promising. Not only does silencing it kill cancer while sparing normal tissue, but an inhibitor for the enzyme it produces already exists: a compound that originally was developed to modulate sleep cycles.
"It had been sitting on a shelf for years, like the thousands of other 'orphan' drugs that are abandoned when they prove ineffective for their intended use," Grandori said.

With a simple, five-minute web search, she purchased the compound online and designed an experiment to test its potential.  She implanted special laboratory mice with Myc-driven neuroblastomas (a deadly cancer of the nervous system that often strikes children), and treated half of them with the new compound. The untreated mice quickly died of their tumors, but the treated mice thrived and their neuroblastomas shrank away.

"It is possible that the next great breakthrough in cancer therapy is already out there, sitting on a shelf, hiding in plain view," said Grandori, who is also a research associate professor and director of the Quellos High Throughput Screening Core at the University of Washington Department of Pharmacology.

Grandori feels that the combination of high-throughput screening and siRNA silencing has the potential to radically change the way cancers are treated.

"We've barely scratched the surface," she said. "These techniques are incredibly powerful, but they're new and not widely known. There are thousands of researchers who could apply this approach to their work. In the right hands, it could speed up the development of new cancer therapies a thousand-fold."

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The Nasa 'space drink' hat can rub out sun spots: Fruit juice developed to protect astronauts reduces wrinkles and reverses the telltale signs of ageing in four months

But does it shorten your lifespan?  Many anti-oxidants do

A groundbreaking study has shown that the concoction, known as AS10, dramatically reduces wrinkles, blemishes and sun damage after four months.

Visia photographs – which reveal the condition of the skin below the surface by using different types of light exposure – were taken of 180 participants at the start of the trial, and again after four months of drinking two shots of AS10 a day. By the end UV spots were reduced by 30 per cent and wrinkles by 17 per cent.

AS10 was developed as a nutritional supplement for astronauts to protect them from the damaging effects of high levels of radiation outside the Earth’s atmosphere.

The drink contains a blend of fruits including cupuacu (a Brazilian fruit from the cacao plant family), acai, acerola, prickly pear and yumberry, which all provide vitamins and phytochemicals – compounds known to block the harmful effects of radiation. Other ingredients are grape, green tea, pomegranate and vegetables.

Radiation particles alter oxygen molecules in the body to create reactive oxygen species (ROS) – so-called ‘free radicals’ which damage cells in a process known as oxidative stress. This process has been linked to diseases such as cancer and Alzheimer’s. The toxic molecules are also thought to play a role in the skin ageing process.

ROS are created naturally within the body as cells generate energy, but also through environmental factors such as chemicals and ultraviolet light from the sun – the strongest stress to skin. Mobile phone radiation, cigarette smoke and alcohol also generate ROS.

‘Think of them as little Pac-men taking bites out of molecules that are essential for cells to function,’ says Dr Aaron Barson, the nutritional scientist from Utah who carried out the AS10 study after patients reported dramatic improvement from the drink.

AS10 is thought to improve skin condition because the drink’s large quantities of antioxidants ward off oxidative stress, allowing the skin to heal naturally. Antioxidants attach themselves to ROS and neutralise them before they cause damage.

Dr Barson says: ‘The skin is the first body tissue to be exposed to UV rays and we know it is sensitive to oxidative stress. Our study shows it greatly benefits from a reduction in this stress. The effects of oxidative stress on the skin can be quickly modified and the skin can heal itself by drinking AS10.’

Dr Barson suggests that the results may have been even better had the trial been conducted during the winter, when exposure to ultraviolet light would have been less.

A second, larger study is planned this summer to investigate for how long the effects last and whether skin condition reaches a plateau or deteriorates once the drink is no longer consumed.

The main drawback is the high price of the drink. The women in the trial drank a sherry glass – 60ml – of AS10 a day. At £30 per 750ml bottle, the cost was just under £300 over the four months.

Cosmetic dermatologist Dr Sam Bunting says: ‘The Visia scans show a marked improvement in the level of UV spots, which represent sun damage beneath the surface of the skin. The kind of interventions that might deliver this level of improvement are glycolic skin peels, which use acids to strip away layers of skin, retinoids, high-potency Vitamin C and hydroquinone with the use of sun block on a daily basis.

‘If these changes were due to AS10, this would be of great interest as UV is responsible for 80 per cent of the skin changes we associate with ageing.’

She adds that although AS10 might well do what it claims, a critical appraisal of the methods in the study would be required to back this up.

Cosmetic dermatologist Dr Mervyn Patterson, of Woodford Medical, agrees. He says: ‘These images show a reduction in the degree of pigmentation on the skin caused by UV exposure. This could be due to the drink.’

But he says daily use of sunscreen with UVB/UVA sun protection factor of 50+ could deliver results on a par with AS10. ‘It is more likely to protect the skin, resulting in reductions in redness and pigmentation and a subtle reduction in wrinkles.’

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