The last decade of research on Alzheimer's disease has been fraught with disappointment.
Years of concentration on a characteristic of the disease have ultimately led to no progress in treatment or prevention.
But next week, when top scientists gather in Los Angeles at the Alzheimer's Association International Conference, many will present research on a different goal: inflammation.
"The big breakthrough is that neuroinflammation is the target.It kills most of the nerve cells responsible for dementia," said Rudolph Tanzi, professor of neurology at Harvard University and director of the Massachusetts Department of Neurology. General Hospital.
Beyond the plates
The first research on Alzheimer's disease was focused on a target: clumps of proteins in the brain called amyloid plaques. When scientists studied the brains of deceased people with Alzheimer's disease, they found that brain tissue was filled with these plaques, which are still considered a hallmark of the disease.
But while research has repeatedly shown that amyloid plaques may play a role in Alzheimer's disease, this is not the only key to treatment.
Indeed, pharmaceutical companies Amgen and Novartis announced Thursday that their trial of a drug intended to block the production of amyloid plaques had failed. In fact, patients who received the drug have worsened. The Alzheimer's Association has qualified the result as "disappointing".
But according to Tanzi, tackling the plates once they are formed means you're too late. This is because amyloid develops very early in the process of Alzheimer's disease – even 20 years before the onset of the first symptoms. "Attacking amyloid in patients already suffering from dementia is like trying to stop a forest fire by blowing up a match," he said. It is the inflammation that allows the fire to become uncontrollable.
"If you want to take the plates, you have to do it early with early detection," Tanzi said. "I think it will be the future to prevent Alzheimer's disease, but for now, how to help the 5 million patients in this country? You need to put out the forest fire."
Turn off the fire
Tanzi is working with a Boston-based company, AZTherapies, to find existing drugs that can combat this neuroinflammation. Tanzi is the director of the company's Scientific Advisory Board and maintains financial ties with the company.
Part of AZTherapies' research is on a drug used to treat asthma, called Cromolyn, which targets inflammation in the lungs. The company has modified the drug so that it reaches the brain and tests it in combination with ibuprofen.
"This is one of the first tests to take a relatively safe drug … let's reformulate it, then ask if we disable neuroinflammation, can we extinguish the forest fire and, like a forest, let it grow back?" Tanzi said.
AZTherapies has recruited nearly 600 patients for this trial and is waiting for the results within a year or two. Still, it's still too early to suggest people take anti-inflammatory drugs to fight dementia. Drugs currently on the market do not reach the brain or cause other risks associated with long-term use, such as increased risk of heart attack, stroke and stroke. ulcer of the stomach.
AZTherapies is not the only company to move away from research on amyloid to focus on inflammation.
Neurotropic will present the research that will take place next week at the Alzheimer's Association conference on its drug, Bryostatin-1.
Bryostatin-1, initially tested as an anti-cancer drug, works by activating a protein involved in the brain's "wiring".
"It induces regeneration of lost wiring and synaptic networks, prevents neuronal death, and is very anti-inflammatory," said Dr. Daniel Alkon, president of Neurotropic.
Alkon told NBC News that in early studies of patients with Alzheimer's disease, those taking bryostatin-1 showed sustained cognitive improvement for at least a month after treatment.
"For us, this is the formation of new networks," said Alkon. "We believe that the way we used anti-inflammatory drugs as part of a comprehensive approach to survival-enhancing brain networks could be a breakthrough for the field."
The fact that inflammation plays a role in Alzheimer's disease is not a new idea – scientists have been studying its role for some time. In 2013, researchers at the Mayo Clinic published a study on post-mortem brains. All brains exhibited amyloid plaques and another hallmark of Alzheimer's disease, tau entanglements.
But only half of the patients had dementia when they were alive. The others were cognitively normal.
"The only thing that differentiated them was an inflammatory response.There were more inflammatory cells in the brain … in people with clinical dementia than in those who were clinically normal, again suggesting that inflammation is a mediator key here, "said Dr. Ronald Petersen. , neurologist at the Mayo Clinic, said.
The search for an effective treatment for Alzheimer's disease will remain crucial as the number of patients – estimated at 5.8 million in the United States alone – is expected to increase to 14 million by 2050, according to Alzheimer's & # 39; s Association. It is the sixth leading cause of death in the United States.
The memory loss associated with Alzheimer's disease can be mild in the early stages of the disease. But over time, patients develop more serious confusion and memory loss, as well as changes in mood and behavior, disorientation, and difficulty speaking, swallowing, and walking.
There is no cure for Alzheimer's disease. The available treatments can only improve the quality of life and temporarily slow down the person's decline.
I have the impression that we finally see a light at the end of the tunnel.
Maria Carrillo, scientific leader of the Alzheimer's Association, is not prepared to call waste the last decade of research on amyloid. On the contrary, she said it helped scientists understand that it was not just amyloid and tau that mattered.
"Today's science tells us that there could be up to four or five other proteins that are not going to help, contributing to the cell death we live in in dementia." 39, Alzheimer's, "said Carrillo.
"It's important that we understand what it is and how to treat it with pharmaceuticals – that's where we need to go, a combined approach that can also include lifestyle changes, like the do other diseases, "she said.
Tanzi agrees. He suggests an approach that he calls SHIELD, an acronym for lifestyle factors that seem to help reduce the risk of developing Alzheimer's disease. They understand:
- good development to sleep habits
- obtain a manipulate on stress
- in interaction with friends
- to do the exercise Daily
- learning new skills
- eat healthy diet
"It's never too early to start thinking about how to protect your brain," he said. He hopes that these lifestyle changes, as well as research on neuroinflammation, will have a marked impact on Alzheimer's disease.
"I have the impression that we are finally seeing a light at the end of the tunnel," said Tanzi. "We made mistakes, but these mistakes taught us where we need to move to the next."
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