By Howard Fillit, MD
Scientists are making exciting headway in the search for a treatment (and even a cure) for Alzheimer's disease.
Earlier this month I joined some of the world's preeminent physicians and neuroscientists in Copenhagen, Denmark, for the Alzheimer's Association's International Conference (AAIC). The six-day gathering is the largest of its kind and featured more than 100 sessions on a diverse range of Alzheimer's topics.
Those sessions represent an incredible amount of new material and research to digest, so I've narrowed down the highlights for those of you who are interested in tracking the latest in Alzheimer's research and drug development:
1. More and more evidence is emerging that modifying lifestyle factors can prevent or delay the onset of dementia from Alzheimer's disease.
Investigators presented high-quality evidence demonstrating that exercise, a healthy diet, moderate alcohol consumption, education and effective management of hypertension, high cholesterol and diabetes can prevent or delay the onset of Alzheimer's and other dementias. In fact, the risk of developing Alzheimer's disease is actually decreasing in developed nations, where individuals are already deploying many of these lifestyle interventions.
2. Two promising immune therapies ("vaccines") may slow cognitive decline and the course of the disease.
While Genentech's phase-three clinical trial of an anti-amyloid antibody therapy for Alzheimer's disease, crenezumab, failed because it did not meet its primary endpoints, an additional analysis suggested it did slow cognitive decline (by over 30 percent) in early-stage Alzheimer's patients. Coupled with results from Lilly's antibody therapy trial in 2012, which also showed a decrease in cognitive decline in early-stage patients, the research provides some indication that clearing amyloid at the earliest stages of the disease may benefit a subset of patients. We'll need further research evaluating larger populations to confirm these findings, some of which is already underway.
3. We can now see Alzheimer's tangles with brain-imaging tools.
Many physicians are currently utilizing FDA-approved brain-imaging tests to detect amyloid plaques in the brains of Alzheimer's patients, but these plaques can be present in individuals who never develop symptoms of the disease. New imaging agents target the tangles (clumps of tau) that are the tombstones of dying neurons and are likely to be a better surrogate for tracking Alzheimer's progression and determining the efficacy of any given drug. Researchers at the AAIC also noted that some of these imaging tools may work for related diseases that also have tangles, such as frontotemporal dementia, and could be used to assess tau pathology in the brain after a traumatic head injury.
4. Treatments that target systemic inflammation offer promise to Alzheimer's patients.
Inflammation increases with aging, and systemic inflammation is increasingly recognized as a risk factor and a driver of Alzheimer's disease. An analysis of data from a previous clinical trial presented at the AAIC showed that patients with markers of high inflammation in their blood responded more positively to a non-steroidal anti-inflammatory drug (NSAID) treatment naproxen (AleveTM), while patients with low levels of inflammation were worsened by the treatment. Another study using the anti-inflammatory arthritis drug Etanercept (Enbrel), in a randomized, placebo-controlled, double-blind phase-two trial, did not meet its endpoints but showed hints of stabilizing cognitive decline in a small subset population.
5. A number of new drugs to treat the symptoms of Alzheimer's disease are in development.
Lundbeck's drug, a 5-HT6 receptor antagonist, was shown to have an added effect on cognitive function when combined with a currently approved acetylcholinesterase inhibitor donepezil. A large, global phase-three study is underway to further evaluate the drug's prospects. Unfortunately, in related news from AAIC, research on an alpha-7 nicotinic acetylcholine receptor agonist drug from AbbVie revealed that the drug was not significantly more effective than existing symptomatic treatments for Alzheimer’s.*
*An earlier version of this blog incorrectly asserted that the negative results came from Forum Pharmaceuticals. This error has been corrected.