NIA Commentary: Translational Issues in Alzheimer’s Disease Drug Development

Abstract

Alzheimer's disease (AD) mainly affects elderly individuals, and because of the aging of populations worldwide, this disorder is reaching epidemic proportions, with an enormous human and economic burden. Effective treatments are urgently needed to treat the cognitive and behavioral symptoms of AD and to slow its progression. The National Institute on Aging (NIA) has developed a number of grant and contract mechanisms to support this effort. The NIA has an exploratory R21 grant program (http://grants.nih.gov/grants/guide/pa-files/PAS-10-151.html) for early AD drug discovery, in collaboration with the Alzheimer's Drug Discovery Foundation, and a program for preclinical drug development of small molecules, biologics, or other compounds for the treatment of AD, mild cognitive impairment (MCI), and age-related cognitive decline, using the U01 cooperative agreement mechanism (http://grants.nih.gov/grants/guide/pa-files/PAR-08-266.html). Examples of funded grants include studies of small molecule neurotrophin mimetics, novel anti-inflammatory compounds, and τ-aggregation inhibitors. The NIA provides investigational new drug-enabling toxicology services for novel AD therapeutic drugs through a contract, which is open to individual investigators or small companies. The NIA also participates in many trans-NIH programs including program announcements for drug discovery for nervous system diseases utilizing the R21 and R01 grant mechanisms, Small Business Innovation Research/Small Business Technology Transfer Research grant programs, and translational programs through the NIH Neuroscience Blueprint (http://neuroscienceblueprint.nih.gov/). The overall goal of these translational research initiatives is to provide support to investigators from academia and the biotechnology sector to increase the number of drug candidates that can be clinically tested. Clinical development can be done through partnership with industry or through NIA-supported clinical trial programs. These include a program announcement for pilot clinical trials (http://grants.nih.gov/grants/guide/pa-files/PAR-11-100.html), large R01 grant applications, and the Alzheimer's Disease Cooperative Study, an NIA-supported clinical trials consortium. Examples of pilot trials include intranasal insulin in people with AD/MCI, and carvedilol in AD, which is an anti-hypertensive drug that was re-purposed for AD, with support from the U01 program. Through these programs, the NIA hopes to facilitate the discovery, development, and testing of new therapeutic agents for AD, MCI, and age-related cognitive impairment. There are very few drugs that have been approved by the Food and Drug Administration for the treatment of AD. There have been many recent clinical trials of potential new therapeutic agents, but none has been shown to be effective in providing symptomatic benefit or slowing disease progression. This indicates the critical nature of the NIA/NIH programs in trying to facilitate getting new therapies out to the patients and families who desperately need them.