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Trying to Solve the Alzheimer’s Puzzle
Despite a 99% failure rate and another major setback last month, Alzheimer’s disease (AD) researchers are pushing ahead with hundreds of experiments—thanks to a surge in federal money—to try to conquer a deadly disease that has confounded them for decades, according to a report from Kaiser Health News.
The 21st Century Cures Act, signed into law by President Obama in December, sets aside $3 billion over 10 years to fund research into brain diseases and precision medicine––a shot in the arm for AD research. The law also includes “prize money” to encourage AD experiments.
So far, however, billions of dollars have been spent over the years, with little progress to show for it. AD affects five million Americans and is the nation’s sixth leading cause of death. Decades of research have not produced a single drug that alters the course of the disease.
December began with another major setback in the AD field: Eli Lilly reported disappointing results from a late-stage clinical trial of its experimental drug solanezumab, which failed to significantly slow disease progression compared with placebo.
But scientists aren’t giving up on the main hypothesis behind Eli Lilly’s trial: that AD can be defeated by using drugs to attack amyloid plaques that build up in the brains of AD patients. Some scientists believe that these plaques cause the disease.
Another promising anti-amyloid drug is aducanumab (Biogen), which improved cognitive decline in a small number of AD patients in an early study.
Other potentially groundbreaking research aims to intervene before patients develop symptoms of the disease. Using positron emission tomography (PET) scans, scientists can now identify amyloid plaques in a patient’s brain years before the patients develop AD. The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) trial is testing Lilly’s solanezumab in adults who are accumulating amyloid plaques but have no signs of AD, such as memory loss or cognitive decline.
Other scientists are targeting what they believe is the true culprit behind AD, the protein tau, which creates “tangles” in the brain, the other primary biomarker of the disease.
These experiments are continuing against a bleak backdrop, however. AD clinical trials have had a 99% failure rate, and no new AD therapies have won FDA approval since 2003. AD patients currently have access to only four FDA-approved rugs. These medications can alleviate symptoms but do not prevent, slow, or reverse brain damage.
Seventy-seven AD drugs are currently being investigated or developed, according to the trade group Pharmaceutical Research and Manufacturers of America (PhRMA). Other studies seek to repurpose drugs that are FDA-approved for other conditions, such as diabetes or cancer, to see whether they can help AD patients—and cut several years off the drug-development process.
Nonpharmacological solutions are also being explored. Observational studies have suggested that people who exercise more and have healthier diets may develop the disease later in life. Researchers are now conducting studies to measure the effects of exercise and diet on AD. For example, the randomized EXERT trial, under way at Wake Forest University, is investigating the effects of high-intensity aerobic exercise on adults with mild cognitive impairment by enrolling them in exercise programs.
Will there ever be a cure for AD? Dr. Ron Petersen, director of the Alzheimer’s Disease Research Center at the Mayo Clinic, isn’t betting on it. “I think slowing the progression and/or delaying the onset are realistic goals,” he said.
Source: Kaiser Health News; January 30, 2017.