As our population ages, the burden of dementia patients grows inexorably. Since 2003, no new anti-dementia drugs have been approved, and numerous phase III drug trials have failed. Biogen and Eisai just ended two late-stage studies. Yet there is reason for hope, writes neuroscientist and psychiatrist William K. Summers, M.D., as he recounts his “winding road” in investigating Alzheimer disease in the spring issue of the Journal of American Physicians and Surgeons.
In the early 1980s, Dr. Summers and colleagues developed and patented the first pragmatic treatment for Alzheimer disease—tacrine. The theory was that by assisting failing neurons that used the neurotransmitter acetylcholine, memory could be improved. This was intended as symptomatic treatment only.
Most of the tens of millions of dollars invested in drug trials since 1980 were based on the amyloid hypothesis or the tau hypothesis. By these theories, the microscopic hallmarks of Alzheimer disease, amyloid plaques and neurofibrillary tangles, were toxic and caused the disease. The new therapies were designed to prevent or clear amyloid plaque or tangles.
Dr. Summers and colleagues, however, view these findings as “tombstones” that mark the location of dead neurons and absorb toxins released as the neurons undergo degeneration. The real cause, they hypothesize, is the oxidative damage that accumulates with age. This operates at many levels, as do the body’s own antioxidant defense mechanisms, which squelch free radicals and promote cellular repair.
A combination of 34 agents that have been shown to cross the blood-brain barrier is patented and marketed as a nutritional supplement. A double-blind trial in normal subjects age 50 to 75 showed significant improvements in memory testing by 30 days and continuing through the 6-month trial in subjects taking the “antiOx” supplement, but not those taking a popular multivitamin.
Dr. Summers presents the case of a patient diagnosed with Alzheimer disease in 2000, who after 3 months on antiOx had an improved Mini-Mental State Examination and began to play golf and bridge again. She did remarkably well for most of 17 years on antiOx, and died at age 97.
Dr. Summers mentions other treatments he has found helpful in managing symptoms of Alzheimer disease and suggests directions for future research.
“The future for treatment of AD and related disorders looks very positive if drug development is re-focused on agents that affect pathogenesis and enhance damage repair,” he concludes.
