Breaching the blood-brain-barrier to improve Alzheimer’s drug treatments

Posted by Biome on 27th November 2013 - 0 Comments


The blood-brain-barrier protects the brain from toxic materials, such as harmful bacteria, but it can also prevent therapeutically important drugs from reaching their target. In Alzheimer’s disease, the most common form of dementia, the low penetration of drugs across the blood-brain barrier is thought to be one of the reasons why many clinical trials have failed. Therapeutic strategies are therefore focused on improving the transport of drugs across this barrier, with one of the most promising avenues of research utilising nanotechnology.

Amyloid-beta precursor protein, which is cleaved by secretases and in Alzheimer's disease can result in amyloid-beta plaques. Image source: RSCB PDB

Vesicles such as liposomes, solid lipid nanoparticles and different polymeric nanoparticles have all been shown to successfully transport drugs across the blood-brain barrier and into the brain. Novel research published in Alzheimer’s Research & Therapy by Claus Pietrzik from the Johannes Gutenberg University, Germany, and colleagues investigated the efficiency of the Alzheimer’s drug flurbiprofen in crossing the blood-brain-barrier when embedded in nanoparticles. Using an in vitro cell culture model of the blood-brain-barrier, they also assessed its biological activity upon crossing this barrier.

Flurbiprofen is an FDA (US Food and Drug Administration) approved drug that has been shown to successfully lower amyloid-beta levels, possibly through affecting the action of gamma-secretase – the enzyme responsible for the production of amyloid-beta. Accumulation of amyloid-beta plaques and neurofibrillary tau tangles are the pathological hallmarks of Alzheimer’s disease. ‘Disease modifying drugs’ such as flurbiprofen act by intervening at a specific point along the pathway of Alzheimer’s neuropathology to counteract the progression of the disease. Currently only symptomatic treatments are approved for Alzheimer’s disease, making strategies focussed on enabling ‘disease modifying drugs’ to reach the brain in high enough concentrations to be effective, particularly important.

The authors demonstrated that flurbiprofen embedded in polylactide-nanoparticles can cross an in vitro model of the blood-brain-barrier and also lower amyloid-beta peptide levels. This illustrates how the modification of usually non-permeable drugs, by embedding in nanoparticles, can result in an efficient transport model across the blood-brain-barrier.

Nanotechnology-based strategies are therefore a promising approach for the generation of novel therapeutic options for Alzheimer’s disease and other neurodegenerative conditions.

 

Research

Nanoparticulate flurbiprofen reduces amyloid-β42 generation in an in vitro blood–brain barrier model

Meister S, Zlatev I, Stab J, Docter D, Baches S, Stauber RH, Deutsch M, Schmidt R et al.
Alzheimer's Research & Therapy 2013, 5:51

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