When will dementia become a curable disease and Alzheimer's a forgotten word?

Article Outline

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This editorial is prompted by persistent questions concerning strategies to accelerate the discovery and development of effective “disease-modifying” interventions for dementia. In this regard, the challenge to the National Institutes of Heath (NIH), the Alzheimer's Association, and pharmaceutical companies is the need for a drastic paradigm shift in the process of: (a) merit evaluation and “risk taking” on unorthodox ideas and (b) translating new discoveries into practical therapies.

Both governmental and nongovernmental entities have explored various mechanisms to accelerate the development of new interventions. However, there is little agreement about the best way to achieve this objective. Nor is there consensus among stake holders in academia, industry, government, the financial community, or families on the precise nature of the barriers to finding a cure for dementia in a timely manner.

The goal of preventing disability or delaying the onset of symptoms has enormous implications for health economics. Progress over the past 20 years in understanding the biology of disease has significantly improved the prospect of attaining this public health objective. Emerging knowledge on the cascade of events that initiate the neurodegenerative process has begun to shift the emphasis of drug discovery efforts toward strategies that modify progression of the disease. Yet while the concept of delaying the onset of disability might appear to be technically feasible, the task of translating basic knowledge on neuroprotection into practical applications is far from simple.

The barriers impeding progress in developing disease-modifying drugs stem not only from the scientific challenges of identifying and validating specific targets for preventive agents, but also from several disincentives for the design and conduct of prevention clinical trials. These hurdles include the high cost of drug discovery research, the lack of adequate research resources, the lack of appropriate models to study the full spectrum of neurobiological and clinical aspects of the disease, regulatory obstacles stemming from the lack of validated surrogate markers of disease progression, lack of validated tools to measure the efficacy of neuroprotective agents in asymptomatic patients, and increasing numbers of risk–averse peer-review groups reluctant to take chances on unorthodox ideas.

The objective of this editorial is to stimulate further debate among knowledgeable stakeholders with differing points of view with regard to factors that influence the pace of progress in Alzheimer's disease drug development. Alzheimer's & Dementia is creating an open forum for dialogue on this topic by inviting “Perspectives” or “Open-Peer Commentaries” on such questions as: What are the critical barriers to drug discovery and therapy development? Are current strategies and resources devoted to the problem adequate to solve the problem? Could these resources be used more effectively to accelerate the pace of progress? Could new or different strategies be adopted to increase the efficiency and productivity of current programs, thus accelerating the pace of progress?

As governmental and private funding agencies are assessing future investment opportunities in research, a critical analysis of the forces that influence therapy development may provide valuable insight into more effective strategies for deploying research resources. The “Perspective” paper by Allen Roses and Ann Saunders in the next issue of Alzheimer's & Dementia proposes a hypothesis aimed at broadening the options for potential new therapy development. The Journal anticipates that this article, along with current and future commentaries, will generate the impetus for other hypotheses or perspectives on improving the prospects of finding a cure.