EU Legislation: Millions of animals spared from chemical safety tests

Tens of millions of animals will be saved from use in chemical safety tests over the next eight years after Europe’s chemical regulator gave the go-ahead to a new streamlined study to assess the safety of substances.

European Union (EU) legislation requires companies to test the safety of the chemicals they produce in two generations of animals to assess the effects on their reproductive systems.

Toxicologists were concerned that the testing requirement would mean up to 54 million animals would be used in chemical safety studies to meet the requirements of REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) legislation introduced in 2007 (see Chemical-safety costs uncertain).

A proposed new test would allow just one generation of animals to be used, with additional tests on a second generation required only if the first round raised concerns.

The regulator, the European Chemical Agency (ECHA), based in Helsinki, had threatened to reject the test saying that there is not yet enough evidence to rely on one-generation testing (see Streamlined chemical tests rebuffed).

But on 15 February, ECHA announced it has now changed its mind in favour of Extended One-Generation Reproductive Toxicity Study (EOGRTS).

The agency says that the streamlined test will “under certain conditions” provide sufficient safety information to replace the two-generation reproductive toxicity study. It says it has already received around 230 proposals from companies to carry out the new test.

The move comes after Nature revealed that chemical companies were not providing the safety data on reproductive and developmental toxicity REACH requires of them. Nature also found that very few companies were proposing to carry out alternative non-animal tests, causing further concern that REACH would boost the number of animals used in toxicity testing.

Toxicologists say that allowing the streamlined test, which is quicker and cheaper to conduct, will encourage more companies to test their products.

New potent and broadly effective antibodies against HIV found

A team of researchers at and associated with the International AIDS Vaccine Initiative (IAVI), The Scripps Research Institute, the biotechnology company Theraclone Sciences and Monogram Biosciences Inc., a LabCorp company, report in the current issue of Nature the isolation of 17 novel antibodies capable of neutralizing a broad spectrum of variants of HIV, the virus that causes AIDS.

The new antibodies, large protein molecules that bind to pathogens and flag them for destruction, were isolated from blood serum samples collected in a continuing global search for broadly neutralizing antibodies (bNAbs) launched by IAVI.

They should provide researchers with a new set of targets for the design of vaccine candidates that can elicit similar antibodies to protect people from contracting HIV. Some of the bNAbs blocked HIV infection of cells as much as 10 to 100 times as potently as previously discovered bNAbs.

“Most antiviral vaccines depend on stimulating the antibody response to work effectively,” said Dennis Burton, a professor of immunology and microbial science and director of the IAVI Neutralizing Antibody Center at The Scripps Research Institute in La Jolla, Calif. Professor Burton, one of the senior authors of the study, is also a member of the Ragon Institute, in Cambridge, Mass.

“Because of HIV’s remarkable variability, an effective HIV vaccine will probably have to elicit broadly neutralizing antibodies. This is why we expect that these new antibodies will prove to be valuable assets to the field of AIDS vaccine research.”

Only a minority of people who are HIV-positive begin to produce bNAbs after several years of infection. Animal studies suggest that such antibodies could block HIV infection if they were elicited by a preventive vaccine.

Researchers prize bNAbs because their structural and biochemical analysis can reveal how to achieve a preventive vaccine. Specifically, scientists expect that they can use information about how bNAbs bind to HIV to construct immunogens—the active ingredients of vaccines—that elicit similar antibodies.

The potency of bNAbs matter because a highly potent antibody could confer such protection at relatively low levels.

“Solving the neutralizing antibody problem is perhaps the greatest challenge facing the field today,” said IAVI’s chief scientific officer, Wayne Koff. “IAVI concluded many years ago that unlocking the information stored in bNAbs was going to be essential to the fulfillment of our mission—ensuring the design and development of broadly effective AIDS vaccines.

This is why we support several laboratories around the world that are designing novel vaccine candidates on the basis of what we’re learning from such antibodies. We have no doubt that these new bNAbs will contribute a great deal to our own immunogen design efforts and, we hope, those of other researchers working on AIDS vaccines.”

In that regard, the new bNAbs are encouraging. Many of them bind hitherto unknown molecular structures, or epitopes, on the surface of HIV. This means that they could significantly broaden the target options researchers have in designing vaccines to elicit similar antibodies.

Read the remainder of the article here

Drug that could reverse Alzheimer’s to be tested on patients

A new drug with the potential to halt or even reverse Alzheimer’s disease is expected to be tested in patients later this year, researchers have revealed.

The drug, which tackles a key factor in the development of the disease, is expected to enter the crucial Phase 3 trial – the last stage before seeking regulatory approval – in the latter half of 2010, according to its inventor, Aberdeen University’s Professor Claude Wischik.

Earlier clinical trials of the drug – called remberTM – showed that it could slow progression of Alzheimer’s disease by 84 per cent over 12 months. Furthermore, the effect was sustained over two years. When the results were reported at a conference in Chicago in 2008, they caused worldwide excitement and optimism that, at last, an effective treatment for dementia could be in the pipeline.

But before the drug could move to Phase 3 trials – which will compare it against placebo in larger numbers of patients – millions of dollars in funding have to be raised and regulatory obstacles overcome.

Prof Wischik is optimistic that that ongoing fundraising will permit the Phase 3 trial to begin this year. “This will be a large-scale, international study using around 50 centres,” he said. “We’re moving on substantially from the Phase 2 trial – we’ve beefed up our management team and have really moved on to another level.

“We’re breaking new ground here – the Phase 2 trial provided the first evidence that a drug of this type could arrest progression of the disease, but we believe it can go further than that and perhaps reverse the disease, at least at its early stages.”

The drug acts on the “tangles” which are found in the brains of people with the disease, and which were first described by Alois Alzheimer in 1907. Around two decades ago, Prof Wischik discovered that these tangles were made up of a build up of tau protein, which destroys the brain cells responsible for memory, before going on to kill neurons elsewhere in the brain.

A university spin-out company, TauRx Therapeutics, based in Singapore, developed a novel treatment from a chemical already used in other conditions, which appears to ‘dissolve’ the tangles and halt cognitive decline – the Holy Grail in dementia treatment.

The Phase 2 trial – intended to reveal side-effects as well as efficacy – revealed that the tested form of the chemical worked well at the low and moderate doses, backing the theory that it could arrest the progression of the disease.

It did not work at the highest dose tested due to a problem with the formulation which affected the release of the drug in its active form and this had an impact both on the efficacy and side-effects and limiting the benefit that can be achieved with the older form of the chemical.

Read the full article here at Caledonian Mercury .....

Zebrafish make good Guinea Pigs

Pic: Morph of Zebra and Tree Frog


Zebrafish need Prozac like they need a bicycle, yet recording how various molecules affect their behaviour may be the perfect way to discover treatments for mental illness and neurological diseases.

Most brain drugs are variations on 50-year-old medicines, says Randall Peterson of Massachusetts General Hospital in Boston, so new ones can't come soon enough.

Because zebrafish have a similar brain chemistry to humans, how they respond to certain drugs might indicate how the same drugs will affect people.

To investigate, Peterson's team exposed zebrafish embryos to thousands of drugs and recorded how each affected their reaction to a flash of light or a slight poke (Nature Chemical Biology, DOI: 10.1038/nchembio.307). Meanwhile, Alexander Schier at the University of Harvard and colleagues measured how various drugs changed the sleep-wake cycles of zebrafish larvae (Science, DOI: 10.1126/science.1183090]).

Both teams found that each drug had its own "fingerprint" in terms of what kinds of behaviour it produced. And drugs with similar fingerprints tended to tweak the same molecular pathways, which suggests zebrafish behaviour is a good indicator for how a drug will change chemistry in the human brain . "I can't tell you what a psychotic zebrafish looks like but I can tell you what a zebrafish treated with an antipsychotic looks like," says Peterson.

Using this approach, the teams identified chemicals that might treat depression, Alzheimer's disease and sleeping disorders.