December 2006: A new cardiovascular drug screening has identified existing anti-hypertensive agents capable of preventing cognitive decline and amyloid neuropathology associated with Alzheimer's disease. The research, conducted by Dr. Gulio Maria Pasinetti at the Mount Sinai School of Medicine in New York, NY, was released today at the American College of Neuropsychopharmacology’s (ACNP) annual conference. These findings suggest that a large number of geriatric patients currently under pharmacological treatment for high-blood pressure with certain anti-hypertensive drugs may also reap the benefits of the drug’s cognitive effects.
Dr. Pasinetti's research is part of a growing push to identify and develop more effective treatments for Alzheimer’s disease. This devastating, degenerative illness is of particular concern now Boomers begin to turn 60 and are at increased risk for developing cognitive impairment and Alzheimer’s disease.
"There is no convincing evidence that there is any available drug presently on the market to cure Alzheimer's disease, and there are many questions surrounding the effectiveness of drugs that are available to delay or effectively alleviate symptoms of memory deterioration or dementia," said Pasinetti. Despite major breakthroughs over the past ten years in understanding the pathogenesis, molecular mechanisms and possible causes of Alzheimer's disease, limited progress has been done in the identification of novel therapeutic strategies that made a real impact in the prevention or treatment of the disease in the general population."
Over the past two years, researchers have begun screening drugs that are already commercially available for treatment of other disorders to determine their potential value in treating Alzheimer’s disease and cognitive impairment.
Commonly prescribed drugs were administered in vitro to brain cells derived from animal models genetically predisposed to develop Alzheimer’s disease amyloid neuropathology. The brain cells in vitro were then monitored to systematically assess the potential beneficial effect of novel drugs, especially in respect to generation of abnormally processed beta-amyloid.
Abnormally processed beta-amyloid has been identified as playing a key role in Alzheimer’s disease pathogenesis, particularly in respect to cognitive deterioration.
Thus, characterization of novel drug treatments preventing abnormal beta-amyloid generation will help in the identification of future, novel pharmacological treatments for Alzheimer's disease.
Among several hundred drugs that were identified in Dr. Pasinetti’s laboratory as having promise in preventing beta-amyloid build-up, seven of the drugs are commonly prescribed to treat hypertension. This recent, promising evidence indicates that cardiovascular anti-hypertensive agents may decrease the incidence or slow the progression of Alzheimer’s disease.
During the course of the research, one drug in particular was identified as effective in blocking the accumulation of beta-amyloid in the brain and preventing the deterioration of cognitive performance. The drug, Propranololo-HCL (Inderal) for example, is widely prescribed in elderly patients to treat high blood pressure. Further research is necessary to determine if these patients may also be benefiting from the potential cognitive effects of the drug.
Pasinetti noted that it might also be possible to identify a concentration of this compound that confers the beta-amyloid blocking benefit without affecting blood pressure.
"If we can give this drug at concentrations that do not affect blood pressure, this drug could be made available for all members of the geriatric population identified as being at high risk for developing Alzheimer’s disease," said Pasinetti.
Pasinetti was quick to point out the limitations of the research, noting that studies must be conducted in human subjects that examine the effects of the drug independent of its role as an anti-hypertensive agent.
"The use of these drugs for their potential anti-amyloidogenic role is still highly experimental, and at this stage we have no clinical data beyond phenomenological observation," said Pasinetti. "We need to complete clinical trials in the future if we are to identify preventive drugs, which will need to be prescribed at dosages that do not interfere with hypertension."