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Alzheimer`s & Dementia
Year: 2013  |  Volume: 9  |  Issue: 2  |  Page No.: 176 - 188

Frontotemporal degeneration, the next therapeutic frontier: Molecules and animal models for frontotemporal degeneration drug development

Adam L. Boxer, Michael Gold, Edward Huey, Fen-Biao Gao, Edward A. Burton, Tiffany Chow, Aimee Kao, Blair R. Leavitt, Bruce Lamb, Megan Grether, David Knopman, Nigel J. Cairns, Ian R. Mackenzie, Laura Mitic, Erik D. Roberson, Daniel Van Kammen, Marc Cantillon, Kathleen Zahs, Stephen Salloway, John Morris, Gary Tong, Howard Feldman, Howard Fillit, Susan Dickinson, Zaven Khachaturian, Margaret Sutherland, Robert Farese, Bruce L. Miller and Jeffrey Cummings    

Abstract: Frontotemporal degeneration (FTD) is a common cause of dementia for which there are currently no approved therapies. Over the past decade, there has been an explosion of knowledge about the biology and clinical features of FTD that has identified a number of promising therapeutic targets as well as animal models in which to develop drugs. The close association of some forms of FTD with neuropathological accumulation of tau protein or increased neuroinflammation due to progranulin protein deficiency suggests that a drug's success in treating FTD may predict efficacy in more common diseases such as Alzheimer's disease. A variety of regulatory incentives, clinical features of FTD such as rapid disease progression, and relatively pure molecular pathology suggest that there are advantages to developing drugs for FTD as compared with other more common neurodegenerative diseases such as Alzheimer's disease. In March 2011, the Frontotemporal Degeneration Treatment Study Group sponsored a conference entitled ”FTD, the Next Therapeutic Frontier,“ which focused on preclinical aspects of FTD drug development. The goal of the meeting was to promote collaborations between academic researchers and biotechnology and pharmaceutical researchers to accelerate the development of new treatments for FTD. Here we report the key findings from the conference, including the rationale for FTD drug development; epidemiological, genetic, and neuropathological features of FTD; FTD animal models and how best to use them; and examples of successful drug development collaborations in other neurodegenerative diseases.

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