Tackling the diseases of old age; progress towards an Alzheimer's therapeutic
S.M. Wilson, J. Patel, S. Dealler, R. Rosedale, C.J. Stanley
PAD Pharma, London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UK
Any major improvements to lifespan are likely to increase the
prevalence of age related diseases such as Alzheimer's Disease (AD). AD
is almost exclusively a disease in those aged 65 or older and the
prevalence increases with age. It is predicted that even with today's
ageing population the prevalence of AD will increase significantly. In
AD the brain has a number of changes that can be linked to pathology
including aggregates of tau and beta amyloid proteins. The amyloid
aggregates, particularly the smaller oligomeric aggregates, have been
linked to toxicity and have been implicated in neuronal death. It is
important to study these oligomeric aggregates in order to find
compounds, potential drugs, which can both prevent aggregation and
perhaps dissociate toxic aggregates that have already formed. We have
developed a ligand, Seprion, that can bind to the aggregates of a class
of protein aggregation diseases including AD, Parkinson's Disease,
Huntingdon's Disease and prion diseases including vCJD in man, BSE in
cattle and scrapie in sheep. The ligand has been built into tests for
BSE in cattle brain (these tests have received USDA and EU-approval),
vCJD in human blood and has been used successfully to differentiate AD
brain from normal brain in a small blind panel of samples. Recently we
have built this ligand into a drug screening assay for compounds that
affect beta amyloid aggregation. The most effective compounds that we
have identified by this screen have been tested in a mouse model of
human AD and have demonstrated a reduction in detergent soluble
aggregates in the brain and a reduction of aggregates as observed by
immunohistochemical analysis of the brain.
Key words:
Alzheimer's aggregates therapy ligand
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