Leading the Search for a Cure for Frontotemporal Dementia

The UCSF Memory and Aging Center is currently leading the first nationwide, multicenter, randomized, placebo-controlled, clinical trial for a potential treatment for behavioral variant FTD (bvFTD) [1] and semantic dementia (SD) [2]. Memantine (Namenda®) is a medication that is currently approved in the US to treat Alzheimer's disease, but a variety of laboratory and clinical data suggest that it may offer some benefit in FTD also.

Dr. Adam Boxer [3] leads the clinical trials program at the Memory and Aging Center.

“Currently, there are no medications that are FDA-approved for the treatment of FTD. Out of desperation, many FTD patients are treated with medications that were originally approved for Alzheimer’s Disease. Unfortunately, there is no good evidence that medications for AD offer any benefit to FTD patients. Our experience and reports from other FTD specialists suggest that some AD medications, such as the cholinesterase inhibitor donepezil (Aricept), may actually exacerbate agitated and inappropriate behaviors in FTD. This may be because cholinesterase inhibitors boost the levels of a brain chemical called acetylcholine that is depleted in AD but not in FTD.

Unlike cholinesterase inhibitors, memantine is thought to work by inhibiting the activity of a receptor (the NMDA receptor) that is present on all neurons and that may have aberrant activity in the setting of a variety of neurodegenerative diseases, including FTD. Furthermore, in AD, memantine helps to ameliorate some of the same difficult behaviors that are present in FTD. Thus we hypothesize that memantine may also be of some benefit in FTD patients.

The only way to determine whether or not memantine is truly beneficial in FTD is to compare patients who are treated with the drug with those who receive a placebo, or sugar pill. By completing this study, we should get a clear answer to this question. In addition, the study will provide us with a wealth of new data on how FTD evolves over time in the experience of different FTD specialists around the country.”

Patients with bvFTD and SD show a progressive decline in behavior and cognitive function as the syndromes advance. Some people develop trouble with their muscles and movement as well. These symptoms can be challenging for caregivers to manage. Currently, several different medications, as well as lifestyle and environmental changes, can help relieve some of the symptoms, but there is no treatment to slow or stop the progressive decline.

This clinical trial will enroll 140 patients at 14 different medical centers across the United States. Each patient will participate for approximately nine weeks, receiving extensive neurological and neuropsychological testing, as well as either the study medication or a placebo. The study is anticipated to conclude in 2009.

If you would like to participate at UCSF, please click here [4]. Other sites collaborating on this project include:

• Case Western Reserve University [5] in Cleveland, Ohio (contact Leon Hudson [6])
• Columbia University [7] in New York City, New York (contact Lynda Mules [8])
• Indiana University [9] in Bloomington, Indiana (contact Julie Dickson [10])
• Johns Hopkins University [11] in Baltimore, Maryland (contact Julia Pedroso [12])
• Mayo Clinic [13] in Jacksonville, Florida (contact Dana Kistler [14])
• Mayo Clinic [15] in Rochester, Minnesota (contact Nancy Haukom [16])
• Northwestern University [17] in Evanston, Illinois (contact Leah Weaver [18])
• University of California, Los Angeles [19] in Los Angeles, California (contact Jill Shapira [20])
• University of North Carolina, Chapel Hill [21] in Chapel Hill, North Carolina (contact Charlene Riedel-Leo [22])
• University of Pennsylvania [23] in Philadelphia, Pennsylvania (contact Lauren Massimo [24])