July 8, 2011 10:20 pm

The cells that are immune to Aids

Scientists in California are turning to gene therapy for a possible cure
Timothy Ray Brown

The ‘Berlin patient’, Timothy Ray Brown, the first man to be cured of Aids, with his dog, Jack

Timothy Ray Brown – better known as the Berlin patient – is a living legend in the world of HIV research, as the first person to be cured of Aids through a medical procedure. The virus was eradicated from the 45-year-old American, resident in Germany, through bone marrow transplants from a donor who had a rare genetic mutation that made him resistant to HIV infection.

Bone marrow transplants from matched donors are far too risky and expensive to become a common treatment for Aids, so ever since the New England Journal of Medicine published a report on the Berlin patient early in 2009, researchers have been looking for a procedure that could mimic the effect without the cost and complexity.

Scientists in California think they have come up with a way to do it – by genetic engineering of the patient’s own stem cells – and they told the BIO conference in Washington last week that they hope to start testing their procedure in a clinical trial early next year.

The innovative procedure, developed by Calimmune, a Californian biotech company with funding from the California Institute for Regenerative Medicine, removes a “doorway protein” called CCR5. HIV uses CCR5 to enter human T-cells, the immune cells that are the primary target of infection. About 1 per cent of people are like Brown’s bone marrow donor, in having a genetic mutation that stops them making CCR5; they are immune to HIV and Aids.

It has recently become possible to extract and amplify stem cells from a patient’s blood, avoiding the need for a bone marrow biopsy. These cells are treated through a genetic engineering technique called RNAi, which permanently stops them making CCR5, and are then infused back into the patient.

The idea is that HIV infection gradually kills off the patient’s original T-cells, which are vulnerable to viral attack. They are replaced by new T-cells, descended from the genetically engineered stem cell infusion, which take over the immune system instead.

Scientists believe this is what happened to the Berlin patient, who is regarded by the Foundation for Aids Research as having achieved a “functional cure”. If the California trial shows that same effect can be achieved through gene therapy of blood stem cells, then Aids patients will be able to stop taking their cocktail of anti-HIV drugs – possibly for ever.

The procedure is far from cheap – and it requires sophisticated medical facilities – so it will not be suitable for most of the world’s Aids patients. But it could still be a money-saver for health providers, given that in the US an average anti-HIV drug prescription costs $25,000 a year or $750,000 over a typical lifetime.

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Wake-up call for sleeping sickness

The first modern drug designed to treat sleeping sickness – a scourge of tropical Africa – is about to be tested in patients.

Sleeping sickness is a classic example of a “neglected tropical disease”, ignored until recently by the western pharmaceutical industry because the market was not large enough in financial terms to justify expensive drug research.

It is caused by a trypanosome parasite and spread by the bite of tsetse flies; left untreated it spreads to the brain, causing sleep disruption, mental deterioration and ultimately death.

Pathogen hunter

Salmonella

Chicken legs

A predatory bacterium called Bdellovibrio kills salmonella in chickens’ guts and could be developed into a “living antibiotic” against pathogens, UK researchers have found.

The outlook changed when the Drugs for Neglected Diseases Initiative – a non-profit organisation dedicated to R&D to bring new treatments to the poorest parts of the world – took an interest.

The development, announced at the BIO conference in Washington last week, came from collaboration between DNDI and two US biotechnology companies, Anacor and Scynexis. Their new drug is a product of Anacor’s unusual chemical approach, incorporating the element boron in compounds to treat a range of fungal, inflammatory and bacterial diseases.

DNDI spent $15m (mainly donated by the Gates Foundation) on a programme to synthesise and test hundreds of boron compounds for their effectiveness against the trypanosome parasite. The one that emerged as the best option will begin clinical trials later this year.

“Due to its safety and efficacy against both stages of the disease, and its ability to be administered orally, this compound could be a breakthrough in the treatment of sleeping sickness and could significantly improve the lives of those who suffer from this insidious disease,” says David Perry, Anacor chief executive.

Current treatments were developed many decades ago. The drugs involved are either highly toxic or difficult to administer in settings where health resources are limited.

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Scales tell tales in Atlantic salmon

Salmon scale

A salmon scale under a microscope

The scales of the Atlantic salmon contain a chemical record of their life history, which can reveal where fish from any river go to feed in the open ocean, research at Southampton University has shown. The results could help protect dwindling stocks of wild salmon.

Salmon scales grow in a series of rings, like tree rings, with most growth taking place when the fish are out at sea. The Southampton scientists measured the ratio of carbon isotopes in the fish scales. This reflects the composition of the food and the water conditions, particularly temperature, where they have fed.

“As every single salmon contains a natural chemical tag, we can now see where fish from individual rivers go to feed in the Atlantic,” says Kirsteen Mackenzie, lead author of the research which is published in the journal Scientific Reports. “We found that salmon born in two areas of the British Isles swim to feeding grounds that are far apart, and experience very different conditions while at sea.”

Analysis of 500 scales showed that salmon from the River Tyne in Northumberland were swimming towards the Norwegian Sea, whereas fish from the River Frome in Dorset were feeding close to Iceland.

In contrast, tagging wild salmon has been an expensive and relatively unsuccessful way to track fish; only 3,000 of the 4m fish tagged in British rivers since the 1950s have been recovered at sea.

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Satellite sinks radio pirates

A scientific satellite has demonstrated the extent of illegal radio transmissions across the world – and led to a crackdown on unauthorised sources.

The European Space Agency’s Soil Moisture and Ocean Salinity (SMOS) satellite, launched at the end of 2009, aims to improve understanding of the global water cycle. It carries a “passive radiometer” that measures microwave radiation emitted from the Earth’s surface in the 1,400MHz-1,427 MHz frequency range, known as the L-band. From this information scientists can deduce the amount of moisture in the land surface and the salinity of the ocean surface.

Regulations from the International Telecommunications Union reserve the L-band exclusively for space science and radio astronomy. All other transmissions are banned.

But the SMOS data quickly revealed serious interference from illegal transmissions, particularly from southern Europe, south and east Asia and the Middle East.

So ESA went into action in collaboration with international and national authorities, which identified many unauthorised transmissions such as television and radio broadcasts, wireless camera monitoring, air surveillance radar and various radiolocation systems.

So far 387 separate sources of interference have been found – and 90 of the worst offenders shut down.

“The problem, although far from being completely resolved, is now much improved,” ESA says.

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