Alzheimer’s treatment within reach, says expert

– The Telegraph (English) –

Professor Simon Lovestone is an academic lead for Alzheimer’s Research UK’s new Drug Discovery Alliance that spans three of Britain’s top universities. The key to prevention of dementia, he tells Virginia Matthews, is early treatment


A simple blood test to predict who will develop Alzheimer’s disease could be the ace up science’s sleeve when it comes to defeating dementia, says Simon Lovestone, professor of translational neuroscience at Oxford University.
After 10 years of research, the professor – also a Lead Academic Scientist at the Alzheimer’s Research UK-funded Oxford Drug Discovery Institute – and his team have identified a combination of 10 proteins which can give early warning of Alzheimer’s, with an accuracy of 87 per cent.
Even though no treatment exists to slow or stop the disease today, this early detection could help turn a corner tomorrow, Prof Lovestone believes.
G8 leaders have committed to finding a cure or a treatment that slows or stops dementia by 2025. As for the deadline, Prof Lovestone is more upbeat than might be expected.

“Although 2025 looks like an enormously difficult target, it is not beyond the bounds of possibility that within the next 10 years, there will be a secondary prevention – made available following a positive blood test and other investigations such as brain scans and spinal fluid tests – but far more substantial investment in research will need to happen before then.”

Prof Lovestone believes that we will find a treatment within 15 years at the outside.
While many of the drug trials of the past have proved discouraging, the professor, who conducted much of his research while at King’s College London, believes that in the majority of them, people have simply been treated too late.
“Alzheimer’s disease is a very long disorder and although typically it can be 10 years from first diagnosis to end stage, it is also now clear that the disease process starts some 10 or even 20 years before any symptoms appear,” he says.
“The blood test we are hoping to develop would both detect people with the disease at this pre-clinical stage, and would allow them to be offered the drug treatments of the future before any symptoms arise.”
In order to be effective, the test will need to be able to distinguish between somebody with early memory problems whose difficulties may not progress, and those whose memory loss is likely to result in dementia.

Invasive testing

While a number of effective biology markers or “biomarkers” have already been identified in Alzheimer’s, the approaches they require are hardly problem-free: the PET brain scan is expensive and not easily available, while the lumbar puncture or spinal fluid test is both uncomfortable and invasive, he says.
“We’re making considerable progress in terms of our blood test and we believe that the clear protein signals we are concentrating on could make it fairly easy to use.
“But I need to stress that while it’ll take a further three to five more years to be sure that it works, it’ll take several more years after that for the test to be available in practice, and only then if a treatment is discovered. Until then, the test should help us in research to find treatments.”
While Prof Lovestone believes that the test could ultimately become part of a suite of biomarkers, with analysis of a person’s blood being followed by a scan and spinal fluid test for further accuracy, he is not yet sure who would opt to come forward.
People of 60 and over who believe they have a particular genetic trait predisposing them to Alzheimer’s would be obvious candidates.
It is also possible that if dementia rates continue to rise, all older people may opt to be tested, but this would depend on whether or not two critical provisos were met first.
“If the drugs of the future can work with people in this pre-clinical phase, then what we are working on today may become a general test, provided the benefits of treatments outweigh the risks of screening.
“But I should also add that there’s really no point in coming up with a blood test at all if people whose tests prove positive still cannot be offered any treatment which works.”
The launch last year of the £30million Alzheimer’s Research UK Drug Discovery Alliance – which will house up to 90 new research scientists across three separate institutes at the University of Cambridge, University College London and Oxford University – promises great things for accelerating the search for treatments for Alzheimer’s and other forms of dementia.
“There are those who have repeatedly said we’re only five years away from an effective disease-modifying therapy for Alzheimer’s but the problem is they’ve been saying it for 15 years.
“It’s true that we haven’t made the progress we expected and this has been hugely disappointing, but it’s also fair to say that this really is an incredibly difficult disease to tackle.”
While Prof Lovestone believes that the failure of clinical trials to date suggests that “either the drugs aren’t good enough or the trials haven’t been good enough”, he says he tends towards the latter view. The reality is that if you already have the symptoms, it could be too late for some of the new drug approaches being tested to slow or stop the disease.
While in some recent trials, he believes up to 20 per cent of the participants either didn’t have the deposits of the hallmark Alzheimer’s protein, beta amyloid, that the drugs are designed to treat, didn’t have some of the known features of Alzheimer’s, or had mild dementia of a different kind.
By contrast, the Oxford research “is highly specific” and, rather than looking at dementia-related disease in general, is seeking out specific blood markers which indicate Alzheimer’s; the most common form of dementia and the one which affects two-thirds of all patients.

Working together

Although the research community could be forgiven for wringing its hands at the lack of apparent progress so far, Prof Lovestone finds the new mood of teamworking between researchers and drug companies to be cause for optimism.
“Via the emergence of some fantastic platforms for the pipeline of new therapies such as the Alzheimer’s Research UK Drug Discovery Alliance and the MRC Dementias Platform UK, scientists and pharma firms have learned that when it comes to discovering more about the early stages of Alzheimer’s, working together is vital.
“Collaboration and open knowledge-sharing in research is really fruitful, and there is a stage of research when it’s possible to do this long before matters of patents, intellectual property and the involvement of lawyers make it difficult. We all benefit and the science moves faster as a consequence.”
He believes that two recent drug trials, by Eli Lilly and Biogen, offer further cause for hope.
“What these very interesting trials show is that if people are going to benefit from this treatment approach, it will be in the very early stage of the disease – as many of us have long predicted.”
For this coming year, the Oxford team will be immersed in yet more biomarker research among the over-sixties – trial participants need to have some degree of memory loss in order to take part – but Prof Lovestone is also looking at the latest frontiers of scientific research.
“For the future, it’s all about the use of new, smart technologies for early detection and that may mean that we are able to use a device worn on the body to monitor people’s walking speed or gait [one of the indicators of cognitive decline] on a constant basis rather than every six or 12 months as now.”

Profound impact

As a clinician scientist, Prof Lovestone has no doubt that the impact of Alzheimer’s on both families and society generally is profound. But he believes that by picking up and acting on signs of failing memory in ourselves and our families and friends more quickly, all of us can play a part in beating it.
“It’s difficult to say how early you need to look out for differences because of the huge variety in individual symptoms and the speed at which they become apparent. But by being attuned to small but significant changes in those we love, we have at least a small chance of helping.”



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Wellbeing | Alzheimer’s treatment within reach, says expert


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