The new research, published in the November 2007 issue of the The Journal of Clinical Investigation., conducted by Dr. Giulio Maria Pasinetti, M.D., Ph.D., Professor of Psychiatry and Neuroscience, Geriatrics and Adult Development and Director of the Center of Excellence for Research in Complementary and Alternative Medicine in Alzheimer's disease at Mount Sinai School of Medicine, suggests that a large number of geriatric patients currently under pharmacological treatment for high-blood pressure with certain anti-hypertensive drugs might reap the additional benefits of the drug's cognitive effects.
"If we can deliver certain anti-hypertensive drugs to patients at high risk to develop Alzheimer's disease, at doses that do not affect blood pressure, these drugs could be made available for all members of the geriatric population identified as being at high risk for developing Alzheimer's disease," said Dr. Pasinetti.
Over the past two years, investigators directed by Dr. Pasinetti at Mount Sinai have been screening more than 1,500 drugs that are already commercially available for treatment of other disorders, to determine their potential value in treating Alzheimer's disease and cognitive impairment.
Based on the outcomes from initial drug screening, Dr. Pasinetti and his collaborators identified 7out of 55 candidate drugs commonly prescribed for the treatment of hypertension, which are capable of significantly preventing beta-amyloid production, which is a major mechanism recently identified as playing a key role in Alzheimer's disease pathogenesis, particularly in respect to promotion of memory loss and dementia. In this new study, Dr. Pasinetti reports that mice genetically determined to develop Alzheimer's disease beta-amyloid production and subsequent cognitive deterioration, significantly benefit from the treatment with the anti-hypertensive agent Valsartan, found to pharmacologically prevent beta-amyloid production in the brain even when delivered to Alzheimer disease mice at doses 3-4 fold lower than the minimal equivalent dose prescribed for the treatment of hypertension in humans. Other anti-hypertension drugs with beneficial results included Propranolol HCI, Carvedilol, Losartan, Nicardipine HCI, Amiloride HCI and Hydralazine HCI.
Showing the use of anti-hypertensive drugs with anti- beta-amyloid production activities in the brain of Alzheimer's disease mice, will help in the identification of future, novel disease- modifying pharmacological treatments for the prevention of cognitive deterioration and eventually dementia in Alzheimer's disease.
Dr. Pasinetti recognizes the limitations of the research, noting that studies must be immediately verified in human subjects to verify the effect of the drugs on cognitive deterioration and memory functions independent of their role as an anti-hypertensive agent.
"The use of these drugs for their potential anti- Alzheimer's disease role is still highly experimental, and at this stage we have no clinical data beyond phenomenological observation in humans" said Dr. Pasinetti. "We need to complete preventive and therapeutic clinical trials in the near future if we are to identify certain anti-hypertensive drugs with anti beta-amyloid antioligomeric activities, which will need to be prescribed at dosages that do not interfere with blood pressure in normotensive Alzheimer's disease patients."
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 for baby boomers beginning to turn 60, at increased risk of developing cognitive deterioration and Alzheimer's disease.