Tracing amyloid in Alzheimer's
14 October 2009
A diagnostic compound that allows researchers to look into the brains of Alzheimer's patients will be used for the first time to gauge the effects of an experimental therapy for the disease.
Called florbetaben, the diagnostic could also provide important insights into the role of beta amyloid, a protein that accumulates into plaques in the brains of patients with Alzheimer's disease and has been shown to be toxic to nerve cells.
The compound is an 18F-radiolabelled tracer that binds specifically to deposits of beta amyloid, and can be measured using positron emission tomography (PET), a nuclear imaging technique which produces a three-dimensional image of functional processes in the body.
In living patients, diagnosis of Alzheimer's currently relies on a mix of cognitive testing and magnetic resonance imaging (MRI) and computed tomography (CT) scans to exclude other forms of dementia, but is only 70 to 80 per cent reliable.
'MRI and CT only allow for the imaging of anatomic compositions of the body, such as organs,' a spokesperson for Bayer Schering Pharma, the company behind the development of florbetaben, told Chemistry World. 'More recently, PET scans are increasingly being read alongside CT or MRI to allow anatomic and structural or molecular information to be gathered at the same time.'
A definitive diagnosis of Alzheimer's relies on the presence of beta amyloid plaques and other hallmarks of the disease in brain tissue samples examined under the microscope.
'A safe diagnosis of [Alzheimer's] is currently only possible post-mortem,' the spokesperson commented.
Data presented earlier this year from a Phase II trial suggested florbetaben could be used to differentiate people with Alzheimer's from healthy volunteers of the same age.
In the latest study, florbetaben will be used to see whether a vaccine developed by Swiss company AC Immune, designed to stimulate the immune system to break down amyloid plaques in the brain, is having the expected effect.
The vaccine has already shown it can reduce plaque size and improve memory in animal models of Alzheimer's disease, according to Dr. Andrea Pfeifer, AC Immune's chief executive.
'Visualising the deposition of beta amyloid that is targeted by our vaccine can be an important parameter for dose selection, and will provide useful complementary data,' she says, adding that developing diagnostics alongside therapeutics is an emerging trend in the pharmaceutical sector.
Meanwhile, florbetaben could also be useful in establishing once and for all the role of beta amyloid in Alzheimer's disease.
In September, Chemistry World reported the results of a study which found that a compound called dimebolin had a beneficial effect on Alzheimer's symptoms, despite increasing levels of beta amyloid. That prompted suggestions that other forms of the protein, such as soluble amyloid oligomers, may be more neurotoxic than plaques.
It may be too soon to reject the prevailing 'amyloid hypothesis', but tools like florbetaben could be invaluable in establishing the role of the protein once and for all.
'A good diagnostic assay should help to evaluate the effect of new treatments in clinical trials better, as well as improve correlation of results with existing pathological and memory markers,' commented the spokesperson.
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