✍ Scribed by Sarah Eagger
No coin nor oath required. For personal study only.
In the mid-1970s, almost simultaneously, three laboratories in the UK discovered low levels of cholineacetyltransferase (CAT) in Alzheimer's disease (AD) (Davis and Maloney, 1976;. This led to the formulation of the cholinergic hypothesis of Alzheimer's disease. The robustness of this finding impressed Professor Raymond Levy. Despite other neurotransmitter deficits, he believed that CAT remained the most consistently and dramatically affected neuroenzyme and the only one to show a clear quantitative relationship with the clinical deficits of the disease . He identified several therapeutic strategies based on this hypothesis. These ranged from genetic engineering and foetal cell transplants through to raising plasma, and hence brain, choline. There were several ways of achieving the latter: by substrate loading with lecithin, inhibiting choline oxidase, inhibiting cholinesterase or using cholinergic agonists. Professor Levy began a systematic programme of research to investigate whether any of these theoretical approaches could benefit clinical practice. His studies on lecithin as a cholineloading strategy (Little et al., 1985) and nicotine as a cholinergic stimulant are well known.
After hearing of Summer's success with the acetylcholinesterase tacrine (THA, tetrahydroaminoacridine) in treating AD, Raymond's curiosity was kindled and, in a letter to The Lancet, he enquired as to how one could procure the drug . This led to contact with another enterprising doctor who had set up his own company, Shire Pharmaceuticals. They could obtain the drug from Canada, and this eventually led to funding being available to
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