Papua New Guinea

Genetic mutation blocks prion disease

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Unknown mechanism helped some people in Papua New Guinea escape historic, deadly outbreak.

A genetic variant protected some practitioners of cannibalism from prion disease.

Scientists who study a rare brain disease that once devastated entire communities in Papua New Guinea have described a genetic variant that appears to stop misfolded proteins known as prions from propagating in the brain1.

Kuru was first observed in the mid-twentieth century among the Fore people of Papua New Guinea. At its peak in the late 1950s, the disease killed up to 2% of the group’s population each year. Scientists later traced the illness to ritual cannibalism2, in which tribe members ate the brains and nervous systems of their dead. The outbreak probably began when a Fore person consumed body parts from someone who had sporadic Creutzfeldt-Jakob disease (CJD), a prion disease that spontaneously strikes about one person in a million each year.

Scientists have noted previously that some people seem less susceptible to prion diseases if they have an amino-acid substitution in a particular region of the prion protein — codon 1293. And in 2009, a team led by John Collinge — a prion researcher at University College London who is also the lead author of the most recent analysis — found another protective mutation among the Fore, in codon 1274.

The group’s latest work, reported on 10 June in Nature1, shows that the amino-acid change that occurs at this codon, replacing a glycine with a valine, has a different and more powerful effect than the substitution at codon 129. The codon 129 variant confers some protection against prion disease only when it is present on one of the two copies of the gene that encodes the protein. But transgenic mice with the codon-127 mutation were completely resistant to kuru and CJD regardless of whether they bore one or two copies of it.

The researchers say that the mutation in codon 127 appears to confer protection by preventing prion proteins from becoming misshapen.

“It is a surprise,” says Eric Minikel, a prion researcher at the Broad Institute in Cambridge, Massachusetts. “This was a story I didn’t expect to have another chapter.”

Collinge and his colleagues are now continuing their work, to figure out the mutant protein’s structure and how it shields against illness.

Future vaccines could be delivered via patch.

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A skin patch that can deliver vaccines cheaply and effectively has been shown off at the TEDGlobal conference in Edinburgh.

Using a patch rather than a needle could transform disease prevention around the world, said its inventor.

Prof Mark Kendall said the new method offered hope of usable vaccines for diseases such as malaria.

Other medical experts welcomed the news, but warned it might be unsuitable for some patients.

Old technology

It was fitting that Prof Kendall delivered his talk in Edinburgh where, 160 years previously, Alexander Wood had lodged the first patent for the needle and syringe.

“The patent looked almost identical to the needles we use today. This is a 160-year-old technology,” he said.

It is also one that, alongside clean water and sanitation, has played a key role in ensuring longer lifespans around the world.

But he said the technology could be overdue for an update.

The nanopatch overcomes some of the more obvious disadvantages of syringe-given vaccines such as needle phobia and the possibility of contamination caused by dirty needles.

But there are other reasons why the method could be transformative, said the professor.

Thousands of tiny projections in the patch release the vaccine, which is applied in dry form, into the skin.

“The projections on the nanopatch work with the skin’s immune system. We target these cells that reside just a hair’s breadth from the surface of the skin,” said Prof Kendall.

“It seems that we may have been missing the immune sweet spot which may be in the skin rather than the muscle which is where traditional needles go.”

In tests at his laboratory in Queensland University, Brisbane, the nanopatch was used to administer the flu vaccine.

Researchers noticed that the immune responses for vaccines administered with the nanopatch were completely different to those given by a traditional syringe.

“It means that we can bring a completely different tool to vaccination,” said Prof Kendall.

The amount of vaccine needed to be effective is much lower, up to one hundredth of the traditional dose.

“A vaccine that had cost $10 [£6.40] can be brought down to just 10 cents, which is very important in the developing world,” he added.

Vaccine failure

Another major shortcoming of traditional vaccines is that, because they are liquid, they need to be kept refrigerated between the lab and the clinic.

“Half of vaccines in Africa are not working properly because refrigeration has failed at some point in the chain,” said Dr Kendall.

When he told the TED audience that the vaccine for the nanopatch could be kept at 23C (73F) for up to a year, he elicited a huge round of applause.

The news was given a more qualified welcome by the British Society for Immunology.

“This approach holds out hope for easy and large-scale vaccination, as it targets a type of immune cell, called the Langerhans cell, that is abundant in the skin,” said Dr Diane Williamson.

“These cells avidly take up the vaccine and are able to kick-start the immune response.

“However, one of the potential issues with skin delivery is transit time and ensuring adequate delivery of the vaccine payload.

“Also there may be issues of tolerability of the patch in some people. However, if these issues can be overcome, the approach does hold out the potential to dispense with conventional needle-based ‘intra-muscular’ delivery.”

The nanopatch will soon begin field tests in Papua New Guinea where vaccines are in short supply.

The country also sees the highest incidence of the HPV virus, which can cause cervical cancer.

Prof Kendall said that while he finds it hard to imagine a world without traditional needles and syringes, he is hopeful that the new method can be widely adopted.

“Let’s hope for a future where millions of deaths a year from preventable diseases can be a historical footnote because of radically improved vaccines,” he said.

Source: BBC

Nautilus stops work on Papua New Guinea deep-sea mine.

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Underwater1_Nautilus.jpgControversial plans to build the first deep-sea mine in Papua New Guinea (PNG) remain stalled, which has prompted the firm behind them to stop building specialised seabed extraction equipment and lay off staff.

A dispute with the PNG government over its equity holding in the project has led Nautilus Minerals to suspend operations, says Michael Johnston, its chief executive officer.

When Nautilus received a licence in March 2011 to mine metal-rich vents called Solwara 1 near New Britain, the government agreed to take a 30 per cent stake in the project and co-finance it.

But the PNG government convened a legal process in June 2012 to determine whether it was obligated to contribute to funding.

“We were paying for it all ourselves and it was becoming too costly,” Johnston tells SciDev.Net. “We were at an expensive stage of the build. We were spending US$3 million or US$4 million a week. For a company of our size, we couldn’t continue to pay for that ourselves.”

Shadrach Himata, deputy secretary of Papua New Guinea’s Department of Mineral Policy and Geohazards Management, confirms that the dispute is about the country’s equity holding in Nautilus.

He tells SciDev.Net that he cannot comment further because he does not want to “pre-empt the arbitration”.

According to Colin Filer, an associate professor at the Australian National University, the Papua New Guinea government has a legal right to take out equity in any company that extracts resources, although it is not obliged to do so.

The previous government, under Prime Minister Michael Somare and acting Prime Minister Sam Abal, preferred to take equity ownership in most projects, he says. The new government, which came to power in August 2011 and retained power after a year-long skirmish with the previous government, has taken a more strategic approach, Filer says.

“It was probably a bad idea for it to contemplate taking an equity stake in something that was technologically and economically a rather risky venture,” Filer tells SciDev.Net.

The Papua New Guinea government has bigger priorities than deep sea mining, Filer says, adding that its main project focus is to produce liquefied natural gas (LNG) for export to Australia.

The first large project in Papua New Guinea led by energy firm Exxon Mobil — a floating LNG production and processing plant plus pipelines — is set to start work in 2014. A second Exxon Mobil LNG project is planned after the first scheme is up and running, he says.

The government cannot pay for all the projects including the mine without seeking credit from other countries, Filer says. Papua New Guinea’s mining rules require the government to ensure that money is available to invest in equity and that projects will make a profit.

The Nautilus project has gained notoriety, prompting questions about its viability and environmental risks and becoming “politically awkward”, Filer says. The government is likely to be hoping that “it will go away”, he says.

Nautilus Minerals may have better luck if it explores the seabed in other parts of the Pacific, such as the Cook Islands, where it faces less political opposition, and then return to Papua New Guinea once it can demonstrate a successful track record, Filer says.

However, PNG’s mining rules limit the period that a company can own a mining tract without working it, he says.

“If it was an attractive project,” he adds, “why can’t the firm get money from the capital markets or find a joint venture partner?”

Despite the setback, the company said in a release last month that it remains committed to “developing the world’s first commercial seafloor copper-gold project and launching the deep water seafloor resource production industry, whilst maintaining an environmentally and socially responsible approach”.

“Nautilus has a highly prospective ground position, which includes 19 identified prospects in Tonga, including the recent high grade discoveries in the NE Lau Basin and a 410 million tonne Inferred Mineral Resource in the Central Pacific,” it said.

Source: SciVx