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July 6, 2012 9:11 pm
The slow but inexorable spread of Alzheimer’s disease through millions of ageing brains is one of the 21st century’s great public health challenges – and research organisations are stepping up efforts to find better treatments than today’s drugs, which offer little more than short-term relief.
The fundamental problem is that scientists still understand little about the underlying processes that destroy the Alzheimer’s brain. Although researchers have known for decades that insoluble proteins build up and poison patients’ brains, they have long wrangled over the relative importance of the two main culprits: plaques of beta-amyloid protein (also known as bap or abeta) and tangles of tau. The dispute between “baptists” and “tauists” is a classic in the annals of academic argument.
Now peace is breaking out, as it becomes clear that the two proteins are essential elements in Alzheimer’s development, and that in the long run, the best chance of preventing the disease or stopping its progress lies in blocking the formation of both bap and tau.
It is unlikely a single drug will successfully block both proteins but biotech companies and academic groups are developing new-wave drugs that target bap and tau individually. In future, these could be combined to make a dual-targeting Alzheimer’s treatment.
At the recent Bio conference in Boston a leading proponent of this approach – AC Immune, a Swiss biotech company – announced a new $418m research and development alliance with its commercial partner Genentech, the biotech arm of Switzerland’s Roche.
The world’s oldest impact crater, a shallow bowl 100km across and formed when a comet or asteroid hit Earth three billion years ago, has been detected in Greenland.
The latest agreement adds a new anti-tau antibody to the companies’ existing $300m programme to produce an anti-abeta antibody, already in clinical trials under the name crenezumab.
“It seems that abeta appears in the brain earlier than tau in the development of Alzheimer’s – well before symptoms appear – but both are linked to later stages of the disease and a cure will need to address both,” says Andrea Pfeifer, AC Immune chief executive.
Crenezumab is about five years ahead of the anti-tau programme. The US National Institutes of Health selected crenezumab for the world’s first attempt to stave off Alzheimer’s in people at high risk of developing the disease. The 300 participants in the $100m NIH trial come from an extended family in Colombia whose members share a rare genetic mutation that typically triggers Alzheimer’s around the age of 45. The trial will show whether or not suppression of abeta plaques in the brain can delay the onset of memory loss and then dementia.
A significant delaying effect from crenezumab could make it an important drug – and a future partner for one of the anti-tau drugs at earlier stages of development.
Stem cell treatment gives sight to sore eyes
Although embryonic stem cells remain a hot political issue on both sides of the Atlantic, only one small biotechnology company is actively testing them in patients.
Last November, Geron stopped the world’s first clinical trial of embryonic stem cells – to repair nerve damage following spinal cord injury – for financial reasons. That left the embryonic field to Advanced Cell Technology (ACT), one of whose products aims to treat various forms of blindness.
Speaking to the FT at the recent Bio conference in Boston, Gary Rabin, ACT chief executive, and Bob Lanza, chief scientist, said the seven patients treated so far – for two progressive eye diseases, Stargardt’s disease and age-related macular degeneration (AMD) – were all doing well.
“Though the primary aim of these ‘phase one’ trials is to assess safety, we are seeing significant improvements in all seven patients,” says Lanza. “There is a real biological signal that the treatments are working.”
The treatment involves injecting retinal cells, grown from embryonic stem cells, into the eyes of people whose own cells have been destroyed by disease. As the new cells grow in the retina, the patient’s sight improves. It is unlikely anyone with advanced disease who is almost blind will have good eyesight restored; but the treatment could arrest the deterioration and preserve good sight for people still in early stages of Stargardt’s or AMD.
ACT’s schedule calls for a total of 36 patients to have been treated by early next year. These will include 12 Stargardt’s patients in the UK. In the US, another 12 Stargardt’s patients and 12 AMD patients will be treated.
The company says one advantage of its embryonic stem cells is that they are all derived from a single cell isolated “non-destructively” in 2005 from an embryo at an early development stage. Other embryonic stem cell lines used for research came from slightly older embryos, which would have been destroyed in the process.
Slow down ageing: get an old dad
Delaying paternity has had a bad press over the years, as more harmful mutations are likely to be transmitted to offspring by older fathers. But now there is some good news: if you avoid one of these disease-causing mutations, you are likely to age more slowly if you have an older father or grandfather.
A study of almost 2,000 people and their parents in the Philippines carried out by scientists from Northwestern University, Illinois, found that children of older fathers inherit longer telomeres. These are the protective DNA caps at the end of chromosomes. Longer telomeres are linked with slower ageing.
The association of paternal age with offspring telomere length is cumulative across multiple generations, so that someone with an older father and grandfather benefits more than someone with an older father and younger grandfather. The results are published in Proceedings of the National Academy of Sciences.
Christopher Kuzawa of Northwestern says evolutionary biology can explain the findings: “If our recent ancestors waited until later in adulthood before they reproduced, perhaps for cultural reasons, it would make sense for our bodies to prepare for something similar by investing the extra resources necessary to maintain healthy functioning at more advanced ages.”
However, the authors said men should not take their study as a recommendation to delay reproduction.
Give it a shot: the nicotine vaccine
A genetic vaccine against nicotine, which could help people stop smoking, has been tested successfully in laboratory mice.
Researchers at Weill Cornell Medical College in New York showed that a single shot of the novel vaccine protected mice against nicotine addiction for their lifetime. The study appears in the journal Science Translational Medicine.
The vaccine contains the genetic sequence of an antibody against nicotine inserted into a harmless virus, together with instructions that direct it to infect liver cells. The liver then acts as a bio-factory, making a steady stream of antibodies that consume nicotine when it enters the bloodstream, preventing most of the chemical from reaching the brain.
“As far as we can see, the best way to treat chronic nicotine addiction from smoking is to have these Pacman-like antibodies on patrol, clearing the blood as needed before nicotine can have any biological effect,” says lead author Ronald Crystal. “Our vaccine allows the body to make its own monoclonal antibodies against nicotine.” Previous vaccines failed because they delivered the antibodies directly and lasted only a few weeks.
“The use of gene therapy to treat ... a non-genetic psychological problem is a concept that would have been unthinkable 10 years ago,” says Robert MacLaren, a stem cell expert at the University of Oxford. “Whilst there may be easier ways of quitting smoking, it could be an exciting concept for other types of drug addiction.”
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