Stuart Lipton offers a new possible reason why all the Alzheimer's drugs have failed.
There are a few commonly trotted out reasons for why virtually every Alzheimer’s drug of the last two decades has failed: Maybe the trials didn’t start early enough in the course of disease, or maybe they didn’t go after the right group of patients?As companies have started earlier and on more select groups of patients, another conclusion has grown increasingly popular: Maybe they’ve all gone after the wrong target. Maybe clearing the misfolded plaques that buildup in patients’ brains, as these therapies have, just wipes away one symptom of the disease but not the root cause.Stuart Lipton, though, has an alternative explanation. A leading dementia expert who helped develop the the last FDA-approved Alzheimer’s drug, he is publishing new research this week showing that the antibodies companies developed might be having an unintended side effect that undercuts any benefit they offer.
“We realized that it’s possible these human trials, many of which have failed, might be in part failing because they’re paradoxically inducing more inflammation in the brain,” he told Endpoints News, “even though they’re getting rid of the protein, which may be a good thing.” "..... They found that if you exposed these microglia to either alpha synuclein, the hallmark misfolded protein in Parkinson’s, the microglia sent off inflammatory signals. And if you added amyloid-beta, the inflammation worsened.
To their surprise, the antibodies successfully binded to the misfolded protein but that didn’t help inflammation. “Rather than make things better, it actually made things worse,” Lipton said.
Again, Inflammation play an important role in Alzheimer's disease!
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