Drugs Aim to Slow, Stop Alzheimer’s Before It Strikes

Researchers try a new strategy to combat disease
Grandfather and Granddaughter

Medical researchers are trying a new strategy to combat Alzheimer’s disease. Instead of treating Alzheimer’s after it develops, scientists are exploring whether certain drugs can stop the deadly, debilitating disease before it starts, or slow its progress.

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Until now, the bulk of medical research focused on treating the disease once it took hold. But researchers now can identify those who are predisposed to Alzheimer’s because of advances in the science behind genetic biomarkers,” says neurologist Jeffrey Cummings, MD, Medical Director at Cleveland Clinic’s Lou Ruvo Center for Brain Health in Las Vegas and Cleveland.

A biomarker is a biological molecule found in blood, body fluids or tissues that is a sign of a condition, disease or an abnormal process.

“Now we can now identify those who are predisposed to Alzheimer’s and start down the path of identifying drugs that may have the potential to prevent the disease altogether,” Dr. Cummings says.

More than 5 million Americans have Alzheimer’s disease, which costs the nation $200 billion in direct health care costs.

As the percentage of Americans older than 65 continues to grow, estimates are that the number of people with Alzheimer’s will nearly triple to 13.8 million in 2050, with health care costs ballooning to $1.2 trillion.

Two of the most prominent clinical trials investigating these drugs right now are the TOMMORROW study and the A4 study.


The TOMMORROW study is evaluating whether the drug pioglitazone can prevent or delay the onset of Alzheimer’s in people who are genetically  predisposed to develop the disease, but have no symptoms of memory impairment.

Pioglitazone is a drug that protects the nerve cells and that has approval from the Food and Drug Administration to treat type 2 diabetes.

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The study is the nation’s largest prevention clinical trial for Alzheimer’s disease, with nearly 5,800 people around the world participating.

The study also will examine whether certain genes in people older than 65 can determine the risk of developing within five years mild cognitive impairment due to Alzheimer’s.

The study will help physicians learn more about the genetic risk of developing Alzheimer’s disease and the benefit of drugs that may prevent the disease. The aim is to help people know their risk of developing Alzheimer’s disease so they can better plan for their future.

The link between type 2 diabetes and Alzheimer’s may be the result of the complex ways that type 2 diabetes affects the brain’s and other body tissues’ ability to use sugar and respond to insulin.

The trial is an example of a repositioning project, in which researchers study an approved drug for a new use or condition.  Repositioning studies aim to accelerate the drug development process and reduce the need to constantly invent new drugs when current treatments could be used in new ways.

The A4 study

The A4 study is evaluating a new drug called solanezumab, which has shown positive results in slowing Alzheimer’s disease progression in tests with more than 1,800 people.

Solanezumab targets a harmful protein called amyloid, which accumulates in brain cells and form plaques. Over time, the plaques impair brain function, usually beginning with memory. Amyloid plaques are one of two hallmarks of Alzheimer’s disease.

Solanezumab is a synthetic antibody that attaches to amyloid as it floats in the brain and removes the protein before it becomes toxic to brain cells.

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Until now, Alzheimer’s disease research has focused on trying to develop drugs that remove amyloid plaques after they are well established. But this hasn’t worked.

The A4 study tests solanezumab in people with elevated amyloid accumulation in their brains, but who have normal thinking and memory.

Having amyloid accumulation doesn’t mean that a person will definitely develop Alzheimer’s. Amyloid accumulation is one of a number of risk factors, including family history and a genetic predisposition.

“If we’re going to be successful in treating Alzheimer’s disease, we have to get amyloid out of the brain as early as possible,” says neurologist Charles Bernick, MD, Associate Medical Director of the Lou Ruvo Center for Brain Health.

The Lou Ruvo Center for Brain Health is participating in the A4 study, which stands for Anti-Amyloid Treatment in Asymptomatic Alzheimer’s.

“We are trying to find out if an anti-amyloid drug given early can change the course of the disease,” Dr. Bernick says.

If the drug proves effective, “it would be a paradigm shift in the way we think about Alzheimer’s,” Dr. Bernick says. “That’s what makes this study so exciting.”


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