The last decade of Alzheimer's disease research has been disappointed.
Years focusing on a characteristic of the disease ultimately resulted in no progress towards treatment or prevention.
But next week, when the best researchers gather in Los Angeles at the Alzheimer's Association International Conference, an annual meeting, many will present research on another goal: inflammation.
"The major breakthrough is that neuroinflammation is the target. It kills the bulk of neurons leading to dementia," said Rudolph Tanzi, professor of neurology at Harvard University and neurologist director at Massachusetts General Hospital.
Moves beyond plaques Early research on Alzheimer's disease pointed to a tangible goal: clumps of protein in the brain called amyloid plaques, When researchers studied the brains of people with Alzheimer's disease who died, they noticed the brain tissue was full of these plaques, which are still considered a hallmark of the disease
But although research has shown time and time again that amyloid plaques can play a role in Alzheimer's, it is not the individual key to cure.
Today, the pharmaceutical companies announced Amgen and Novartis that their attempts at a drug that would contribute To block the production of amyloid plaques had failed, in fact, patients who got the drug got worse. The Alzheimer's Association called the result "depressing".
But according to Tanzi, who goes after the plaques after they have been formed, it means that you are too late. This is because amyloid develops very early in Alzheimer's disease – even 20 years before the first symptoms occur. Attacking amyloid in patients who already have dementia is like trying to stop a forest fire by blowing out a match, he said. It is inflammation that makes the fire out of control.
"If you want to hit the plaque, you must do it so early with early detection," said Tanzi. "I think it will be the future to prevent Alzheimer's disease. But how can we help the 5 million patients in this country? You need to put out the forest fire."
Postponement of Inflammation Fire
Tanzi works with a Boston-based company called AZTherapies to find drugs that already exist that can cope with the neuroinflammation. Tanzi serves as head of the company's scientific advisory board and has financial links with the company.
Part of AZTherapie's research involves a drug used to treat asthma, called Cromolyn, which targets inflammation of the lungs. The company changed the medicine to reach the brain and tested it in combination with ibuprofen.
"This is one of the first attempts to take a relatively safe drug … reformulate it and then ask if we reverse neuroinflammation, can we lay out the forest fire and, like a forest, let it grow back?" said.
AZTherapies has reported nearly 600 patients for that trial and expects results within the next year or two. Yet, it is far too early to suggest that people take anti-inflammatory drugs to ward off dementia. Drugs on the market either do not reach the brain or with other risks associated with prolonged use, such as increased risk of heart attack, stroke and ulcer.
AZTherapies is not the only company moving from amyloid research into inflammatory areas.
Neurotrope will present research at next week's Alzheimer's Association on its drug, bryostatin-1.
Originally tested as a cancer drug, bryostatin-1 works by activating a protein involved in the "conduction" of the brain.
"It induces the regeneration of wires and synaptic networks that are lost. It prevents neuronal death, and it is also very significantly anti-inflammatory," said Dr. Daniel Alkon, President of Neurotrope.
Alcon told NBC News that those who took bryostatin-1 in early studies of Alzheimer's patients showed cognitive improvement lasting at least one month after treatment.
"For us, this is compatible with new network work being formed," said Alkon. "We believe that the ways in which we have used anti-inflammatory drugs as part of an overall survival strategy in the brain's network can be a breakthrough for the field."
That inflammation plays a role in Alzheimer's not a new idea – researchers have studied their role for some time. In 2013, researchers at the Mayo Clinic published a study that considered post-mortem brains. All brains had evidence of amyloid plaques and another Alzheimer's characteristic, rope tangles.
But only half of the patients had dementia when they lived. The others were cognitively normal.
"The only thing that separated them was an inflammatory response. There were more inflammatory cells in the brain … in those people who had clinical dementia compared to those who were clinically normal, again indicating that inflammation is a key mediator here ", says Ronald Petersen, a neurologist at the Mayo Clinic.
The search for effective treatment of Alzheimer's disease will remain crucial as the number of patients – estimated at 5.8 million in the United States alone – is forecast to swell to 14 million by 2050, according to the Alzheimer's Association. It is the sixth leading cause of death in the United States
Memory loss associated with Alzheimer's may be mild in the early stages of the disease. But over time, patients develop more serious confusion and memory loss as well as mood and behavioral changes, disorientation, and difficulty speaking, swallowing, and walking.
There is no cure for Alzheimer's disease. Available treatments can only improve the quality of life and temporarily lower a person's decline.
I feel like we finally see a light at the end of the tunnel.
Maria Carrillo, Chief Scientist at the Alzheimer's Association not ready to call the last decade of research on amyloid a waste. On the contrary, she said it has helped scientists understand that it is not just amyloid and rope that means it.
"Today's science says there can be as many as four or five other proteins that go wrong, which contributes to the cell death we experience in Alzheimer's dementia," says Carrillo.
"It is important that we understand what they are and how to handle them all with drugs. This is where we have to go, a combination that can also include lifestyle changes, just like other diseases do, "she said.
Tanzi agrees, proposing an approach he calls SHIELD, a lifestyle factor acronym that seems to contribute to reduce the risk of developing Alzheimer's, including:
developing a handle on stress
interacting with interacting with with friends
I feel like we finally see a light at the end of the tunnel.
"It's never too early to start thinking about how to protect your brain, "he said. He is hopeful, the lifestyle changes, plus research on neuroinflammation, will have a noticeable impact on Alzheimer's disease." "I feel we are finally seeing a light at the end of the tunnel," Tanz i. "We've made mistakes, but those mistakes have taught us where we need to come to the next."
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