Huddled around conference tables in an $80-million building designed by the star architect Frank Gehry, some 65 representatives from academia, industry, advocacy groups, and government agencies met 25-26 March 2011 for dialogue whose concentrated intensity evoked the neon glare of the Las Vegas strip just a few miles south. Their discussions tried to illuminate a path toward treatments for frontotemporal dementia (FTD). FTDs afflict 200 times fewer people than does Alzheimer’s disease, but lead to death sooner and are as common as AD in people 65 or younger. Many FTD patients are still misdiagnosed as having AD or a psychiatric disorder, and frontotemporal dementias have as yet no specific therapies.

However, recent research advances have ignited the field—so much so that last year a handful of academic and pharmaceutical scientists launched a study group to speed drug discovery for these rare disorders. The FTD Treatment Study Group (FTSG) met for the first time in April 2010 at the annual meeting of the American Academy of Neurology in Toronto, then again in October at the 7th International Conference on Frontotemporal Dementias in Indianapolis, Indiana. Last month, the fledgling organization held its first independent meeting, “Frontotemporal Dementia: The Next Therapeutic Frontier,” in Las Vegas.

The conference took place at the Cleveland Clinic Lou Ruvo Center for Brain Health, whose 18,000 curving stainless steel shingles and 199 uniquely shaped windows arguably make it a Lady Gaga among neurodegenerative disease facilities. “You’re in one of the greatest buildings in the world,” director Jeffrey Cummings told attendees. “At this meeting, we should have thoughts commensurate with this building.” To facilitate outré thinking, Cummings and others on the FTSG steering committee packed the one-and-a-half-day agenda with talks on preclinical animal models for FTD and lessons from collaborative therapeutic initiatives in other neurodegenerative disorders, and spiced up discussion with proposals ranging from a Web-based registry of FTD models to an independent clearinghouse for deciding which compounds should get tested in which models. The organizers are summarizing conference proceedings in a position paper to be published in a peer-reviewed journal. In anticipation of this detailed, formally referenced article, this story briefly recaps the key science reported in Las Vegas. See upcoming Part 3 for the collaborative drug discovery proposals and pharma’s response to them, and Part 1 for a broader vista on the Lou Ruvo Center and its mission to rejuvenate clinical studies of neurodegenerative disease.

Along with Cummings, the FTSG steering committee consists of Susan Dickinson, Association for Frontotemporal Degeneration; Howard Feldman, Bristol-Myers Squibb; Howard Fillit, Alzheimer’s Drug Discovery Foundation; Michael Gold, Allon Therapeutics; and Megan Grether, Bluefield Project to Cure Frontotemporal Dementia. Adam Boxer, University of California, San Francisco, chairs the committee and organized the scientific component of the recent meeting.

Nine pharmaceutical companies sent representatives to Las Vegas. Boxer explained why their industry should find it in their interest to invest in FTD. Beyond the incentives that come with FTD’s orphan drug status and new diagnostic criteria, frontotemporal dementias progress rapidly—much quicker than AD, whose slow progression has made trials on this disease long and costly. “Theoretically, one could do a shorter trial and have greater power to detect an effect,” Boxer said. People with FTD also tend to be younger and have fewer comorbidities than AD patients. Furthermore, Boxer noted, some FTD syndromes have a clearer link to specific molecular pathology than in AD, where a mixture of amyloid, tau, synuclein, and even TDP-43 pathology may contribute to the clinical phenotype. In this regard, FTD with parkinsonism linked to chromosome 17 (FTDP-17) and progressive supranuclear palsy (PSP)—both pure tauopathies—rank among the top FTD treatment candidates, Boxer said. Another is progranulin-related FTD, which looked therapeutically promising in a subsequent presentation by Fen-Biao Gao, University of Massachusetts Medical School in Worcester.

Full Story

• Part 1—Las Vegas: Lou Ruvo Center Pioneers New Approach to Clinical Trials
• Part 2—Las Vegas: Are Frontotemporal Dementia Models Fit for Pharma?
• Part 3—To be published