November is National Alzheimer’s Disease Awareness Month and National Caregiver Month.

In the United States, Alzheimer’s disease is the sixth leading cause of death, and currently, more than 5 million Americans are living with the disease.

As people are living longer across the U.S., doctors unfortunately are diagnosing more and more people with this slowly progressing, memory-robbing disease. A few well-known sufferers of Alzheimer’s such as President Ronald Reagan, singer Glenn Campbell, and esteemed women’s college basketball coach Pat Summit have helped raise public awareness for the disease over the last several decades. Coming out publicly about their illness has led to an increased effort towards finding a cure for the millions of people faced with a similar fate.

Sadly, 19 years since President Reagan shared his own diagnosis with his fellow Americans, there is still no cure for the disease.

A Sign of Hope

Over the last few years, the medical research community has realized that a new paradigm is emerging for the development of new treatments for Alzheimer’s disease. Although early intervention sounds like a very good idea for any disease, this is not easy when “early intervention” may mean treating people many years before they have recognizable symptoms of the disease. However, in an attempt to develop new treatments for Alzheimer’s, this is what researchers intend to do.

Alzheimer’s disease develops when plaques, which are microscopic clumps of protein deposits, accumulate in the brain. They consist primarily of β-amyloid peptide aggregates and have been recognized for years as a key feature of Alzheimer’s disease. This has allowed for the development of a number of drugs that inhibit several of the biochemical processes that lead to amyloid formation and deposition. While some treatments have made it into clinical trials, the results have been disappointing. Several potential treatments have made it all the way to phase 3 studies, only to fail in the demonstration of efficacy.

Many have speculated that these treatments failed because they were tested too late in the disease process. It takes years, if not decades, for amyloid deposition to occur. Currently, researchers use the detection of memory deficits by interviews and cognitive testing to diagnose Alzheimer’s disease. The disease process may have advanced beyond the point where our current drugs can alter the disease course sufficiently to create a signal in a clinical trial if we wait until the symptoms of memory loss are clinically detectible. If potential treatments were tested at earlier stages of the disease, we might be able to see efficacy demonstrated; however, we don’t have a method for accurately identifying patients before they show measurable symptoms.

Academia, regulators, and industry professionals are now working on several major initiatives to change how treatments for Alzheimer’s disease are developed and tested. FDA has recently given industry guidance for designing and executing clinical trials involving patients who do not present with dementia.

Some researchers are considering the FDA’s accelerated approval mechanism in trials where patients present even earlier clinical stages of Alzheimer’s on the basis of cognitive assessments alone. Drugs that address an unmet medical need may be approved on the basis of a surrogate end point or an intermediate clinical end point (e.g., a sensitive cognitive measure) using the accelerated approval mechanism. This regulatory strategy is especially promising for treatments that appear to be effective in early Alzheimer’s disease, when patients might be expected to derive the greatest benefit.

To help with this new approach, The National Institutes of Health (NIH) recently announced approximately $45 million in new funding to support research initiatives that will test drugs aimed at Alzheimer’s prevention and identify novel biological targets.

The continued attention, research initiatives, and new funding dedicated to Alzheimer’s research holds promise for developing effective treatments and finding a cure in our lifetime.