Subdural Pharmacotherapy Device Adapted to the Treatment of Alzheimer ’ s Disease

semanticscholar(2015)

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Citation: Nandor Ludvig. “Subdural Pharmacotherapy Device Adapted to the Treatment of Alzheimer’s Disease”. EC Neurology 1.S1 (2015): S1-S5. According to the World Alzheimer Report 2014 [1], dementias, mostly Alzheimer’s disease (AD), affect about 44 million people worldwide with the global annual costs exceeding $600 billion. Yet, none of the approved drugs for AD is effective to even significantly alleviate its devastating cognitive symptoms. To change this “flat line of progress” in AD therapy [2], the following fundamental problems of systemic (e.g., oral, intravenous, transdermal) drug treatments for dementias need to be considered. First, drugs that can improve the efficacy of deficient neurotransmitter systems (e.g., the cholinergic system) cause often severe systemic side-effects when given systemically in effective doses, due to the unnecessary distribution of these drugs in the entire body. Second, potentially beneficial neurotrophic proteins, such as Nerve Growth Factor (NGF) or Brain-Derived Neurotrophic Factor (BDNF), do not cross the BBB upon systemic administration in pharmacologically significant quantities. Third, even those compounds that cross the BBB cannot be selectively directed via systemic administration to the hippocampal – association memory circuitry responsible for the predominant symptom, memory impairment, of AD. Fourth, no systemic drug application can clear the hippocampal–association cortical extracellular space from the wide spectrum of potentially neurotoxic molecules ranging from amyloid beta oligomers and proinflammatory cytokines to excess glutamate and extracellular tau.
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