Bold new steps in untangling the treatment of Alzheimer's disease

Bold new steps in untangling the treatment of Alzheimer's disease.
Since the discovery of the apolipoprotein E gene variant (ApoE4) in 1993, the state of the science has been that ApoE4 in connection to β-amyloid plays the leading role in triggering onset of Alzheimer's disease and illness. Presence of the gene variant coveys a 4-fold risk of contracting the condition.

Seminal data recently published in Nature (Sept 2017) now suggests a brand-new mechanism. While there is continued belief that ApoE4 exacerbates initial amyloid pathology, it is thought that its most toxic effects may result from a damaging innate immune response to a different protein called tau.1, with protein deposits called ‘tau tangles’ creating continued damage.



The study reveals that both β-amyloid plaques and tau tangles represent equally important targets for treatment. While current treatment can clear β-amyloid plaques, this doesn’t reverse or prevent memory loss. Several new β-amyloid targeted drugs are in phase III development. These include aducanumab, a monoclonal antibody targeting aggregated forms of β-amyloid, and JNJ-54861911, a beta-secretase inhibitor, the enzyme that makes β-amyloid.>

Immunotherapy may be one way to stop tau tangles from spreading by using antibodies to prevent the seed of one misfolded protein from traveling to another. Drugs based on salsalate, a clinically used derivative of salicylic acid, which are inhibitors of tau acetylation and aggregation are being actively pursued in phase III studies based on impressive results in animal studies.

Both β-amyloid plaques and tau tangles cause an immune response in the brain, and microglia cells act as the first form of immune defence against them. Drugs in late stage development include sargramostim, which targets inflammation, and pimavanserin, which is an inverse agonist for the 5-HT2A receptor, which is found on the surface of many neurons that are involved with awareness and thinking.

For more information and the latest data on HCP use of social and digital media, please get in touch cliff.wyatt@hexagonmedcomms.co.uk.





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