While Alzheimer's disease immunotherapies have been able to prevent the tangles of amyloid beta (Aβ) protein deposits developing in the brain, Eli Lilly ($LLY) has gone a step further. According to a paper in the Cell Press journal Neuron, one of the pharma company's antibodies has cleared existing plaques in a mouse model of Alzheimer's disease.
Studies show that previous antibodies against Aβ in mice have been able to reduce or stop the buildup of the Aβ plaques. However, the same antibodies given to mice that already have plaques in their brains seem to set off severe side effects, including small bleeds in the brain known as microhemorrhages.
The researchers at Lilly have created a tweaked antibody that targets just the insoluble Aβ that makes up the plaques rather than the circulating soluble form of the protein. In mice given shots of the plaque-specific antibody, their Aβ tangles were cleared with no side effects. However, the mice that had the less-specific version of the antibody had no clearance of plaque and bleeding in their brains, perhaps because the antibodies were saturated with the free-floating form and so couldn't target the insoluble form.
"The data suggest that an antibody that binds to only insoluble amyloid beta is likely critical for plaque removal without the associated adverse event of microhemorrhage. These findings have important implications for current and future development of antibodies for the treatment of Alzheimer's disease," first author Ronald DeMattos of Lilly said in a statement.
This may be behind the failure of Pfizer ($PFE) and Johnson & Johnson's ($JNJ) Phase III Alzheimer's drug, which targets both soluble and insoluble Aβ, and which was scrapped in August after its results fell short.
Despite many years of research, Alzheimer's disease is still somewhat of a mystery, with therapeutics on the market only dealing with symptoms rather than slowing, stopping or even reversing the course of the disease, the real goal. Amyloid plaques appear to develop up to 10 years before symptoms appear, so tying together a biomarker that can detect the disease in its early stage with a therapeutic that may be able to halt and reverse the plaque development before it does any long-lasting harm would be the holy grail.
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