September 16, 2010

Medication Used For Diabetics May Treat Patients With Alzheimer’s Disease

(Ivanhoe Newswire) -- A new treatment for patients with Alzheimer's disease may be a medication used to help diabetics.

"Alzheimer's disease is an immense and growing public health problem," which the authors of the pilot study were quoted as saying.  "Although prescription drug therapy for the symptoms of Alzheimer's disease has been available since 1993, these agents do not fundamentally alter the pathological expression of the disease or its progressive course.  The failure of several recent treatment trials directed at the beta-amyloid peptide, a key pathological correlate of Alzheimer's disease, suggests a need to explore alternative approaches to Alzheimer's disease treatment that are not focused on beta-amyloid metabolism."

The nuclear receptor peroxisome proliferator (activated receptor gamma / PPAR-gamma) -- which acts to regulate glucose and lipid metabolism -- may be another potential therapeutic target for the treatment of Alzheimer's disease.  Originally developed for patients with type 2 diabetes, thiazolidinedoines, a common medication used to reduce insulin resistance, triggers a response of PPAR-gamma in patients with Alzheimer's disease.  David S. Geldmacher, M.D., of the University of Virginia Health System, Charlottesville evaluated the safety of one of these medications, pioglitazone, in patients not with diabetes but with Alzheimer's disease through an 18-month, double-blind, placebo-controlled randomized controlled trial.  A total of 25 -- out of the 29 who were chosen for the trial -- completed all 18-months.  12 of the patients received 45 milligrams of pioglitazone daily and remaining 13 received the placebo along with 200 international units of Vitamin E.

The main adverse event in the trial which affected four patients in the pioglitazone group (28.6 percent) was peripheral edema or swelling of the legs and feet.  "This is consistent with the known adverse event profile of pioglitazone," the authors added.  "No group differences in laboratory measures were identified."

"No significant treatment effect was observed or exploratory analysis of clinical efficacy," the authors said.  Furthermore, the study was not intended to determine treatment efficacy.  The authors concluded that a study enrolling 155 to 340 participants randomly assigned to one of the two aforementioned groups would need to be enrolled in order to justly treatment effects for patients with Alzheimer's disease.

"Disappointing results of treatment trials was based on the amyloid hypothesis, and the reasonable degree of safety identified in this trial, suggest that exploratory studies of thiazolidinedoines remain warranted," the authors concluded. "Future studies of this class should focus on earlier stages of disease progression and be augmented by biomarkers, such as nuclear imaging techniques, to measure changes in microglia activation associated with treatment.

SOURCE: The Journal of the American Medical Association: Archives of Neurology, January 2011