For decades, scientists have been trying to figure out how Alzheimer’s disease does its damage so that they can determine how it might be treated. A hallmark of the disease is the globs of protein that form in the brain. There’s mounting evidence that “part of what damages the brain is the body’s own immune responses to these abnormal proteins,” Standaert says. Various anti-inflammatory drugs have been trialed in Alzheimer’s patients, but with disappointing results.
Etanercept reduces inflammation by blocking a protein called tumor necrosis factor (TNF), which plays an important role in immune responses. TNF occurs naturally in the brain, but studies have found elevated levels in people suffering from Alzheimer’s disease.
Recent evidence suggests that TNF regulates the activity of synapses, which connect brain cells and enable electrical signals to travel around the brain. In Alzheimer’s patients, an excess of TNF may wreck havoc on those connections, Tobinick says. “Even though the neurons may be working, the connections between the neurons and between the different lobes of the brain may not be working properly.”
By using etanercept to reduce levels of TNF in the brains of Alzheimer’s patients, Tobinick thinks he may have normalized those connections, leading to an immediate improvement in cognitive functioning. He says that he’s working with academic partners to design larger-scale trials of the treatment. However, Sonia Fiorenza, a spokeswoman for Amgen, which markets Enbrel, says that the company won’t be sponsoring trials because it doesn’t believe there’s enough evidence that it may be useful in Alzheimer’s disease.
Some researchers want to see independent studies carried out, in part because Tobinick has disclosed that he has stock in Amgen and holds patents on the use of the drug and other anti-TNF agents to treat Alzheimer’s disease.
It’s not unusual for researchers to have a financial interest in something they’re studying, Thies says, and “it doesn’t stop them from doing good science.” However, “you’re going to have to have some independent confirmation in the hands of others.”
“You have to do these [studies] double blind, placebo controlled, by people who don’t have a financial interest,” says J. Wesson Ashford, a senior research scientist at the Stanford University/VA Aging Clinical Research Center. (He was not involved in Tobinick’s work.) “I’d really like to believe it, but I’ve seen it so many times, when people say something and it doesn’t turn out to be anything.”
“This is something that’s got to be looked at,” Griffin says. “I hope that scientists will pay attention to this, and the funding agencies will pay attention to this.”
“This is not a cure,” she adds, but if there’s a person who can’t dress or feed himself, is arrogant, mean, and up all night, “and you can take them to the point where they can feed themselves, they’re calmer, attentive, conversational–in other words, you can stand them–that’s great.”