MADRID – Leuprolide acetate may help forestall functional decline in patients with mild to moderate Alzheimer's disease, Christopher W. Gregory, Ph.D., reported in a poster at the 10th International Conference on Alzheimer's Disease and Related Disorders.
The drug, most frequently used for prostate cancer, endometriosis, and precocious puberty, decreases levels of luteinizing hormone–an action that has been shown to decrease the rate of cognitive decline and amyloid accumulation in an Alzheimer's mouse model. Anecdotal evidence has suggested that leuprolide acetate also boosts cognition in some men taking it for prostate cancer, said Dr. Gregory, vice president of research for Voyager Pharmaceutical Corp.
“Our hypothesis is that elevations in luteinizing hormone levels, which are a result of normal aging, may contribute to several of the pathologic processes that foster the development of Alzheimer's” including promoting tau phosphorylation and amyloidogenic processing of the amyloid precursor protein, Dr. Gregory said in an interview. “Therefore, reducing luteinizing hormone levels may help to improve the symptoms of Alzheimer's.”
He presented the results of a phase II pooled data analysis in which 106 men and women with mild to moderate Alzheimer's received either leuprolide acetate (22.5-mg injections given every 12 weeks) or placebo for 48 weeks. About 75% of the patients were on acetylcholinesterase inhibitors, which were continued throughout the study.
After 48 weeks, compared with placebo patients, those in the active group retained significantly more function in both activities of daily living (mean change from baseline −5.4 placebo vs. −3.5 leuprolide) and global function (unchanged or improved from baseline, 34% placebo vs. 51% leuprolide acetate).
Leuprolide patients also experienced less cognitive decline than did placebo patients (about 2 points), although the difference was not statistically significant.
The results were encouraging enough for the Raleigh, N.C., company to launch two 56-week phase III trials of leuprolide implants vs. placebo. Each study will need 555 patients with mild to moderate disease. All patients must have been taking an acetylcholinesterase inhibitor for at least 120 days prior to baseline.
The conference was presented by the Alzheimer's Association.