The Alzheimer’s Association offers the Part the Cloud Translational Research Grant Program, which aims to fill the gap in Alzheimer’s disease drug development. The program supports early phase studies of potential Alzheimer’s therapeutics or validation of biological markers of disease progression and moves us closer to potential therapies to stop or slow the progression of Alzheimer’s. More information is available at alz.org/grants.
There is no greater health care need than slowing or preventing Alzheimer’s disease. The vast increase in understanding of the neurobiology of Alzheimer’s in recent decades, from genetic factors to amyloid accumulation, tangle formation, cellular dysfunction and synaptic failure, has led to the identification of highly promising targets for new therapies. Among the therapeutic strategies being pursued are beta and gamma secretase inhibitors to reduce amyloid production, immune-therapeutics to increase clearance of amyloid, immune-therapeutics targeting tau pathology and various approaches to protecting brain cells from neurodegeneration.
However, the process of developing candidate therapies is long and complex. The steps from target identification to the clinic includes high-throughput screening, lead optimization, establishing target engagement in vitro and in vivo, assuring central nervous system penetration, animal toxicology and, finally, the three phases of human testing. The full process takes many years and substantial resources and typically involves different groups of investigators at different stages.
While many academic investigators and companies have discovered candidate therapeutics and have succeeded in the preclinical stages of development, moving into human testing can be a major stumbling block. Most government and non-government grant mechanisms support preclinical development or mid- to latter-stage clinical trials testing drug efficacy in humans, but there are few mechanisms for supporting the critical earlier human phase studies. At present, the National Institute on Aging supports many phases of preclinical Alzheimer’s drug development, including basic research on target identification, animal model testing of candidate therapeutics, preclinical toxicology and proof-of-concept (POC) studies in humans. These human studies must be preceded by smaller, early phase studies, but there are few appropriate mechanisms to fund the next step: Phase 1 trials in humans. This new grant program from the Alzheimer’s Association was developed to meet that need.
Novel compounds are typically introduced into humans through a series of small Phase 1 studies: single and then multiple ascending-dose studies in healthy adults to assess pharmacokinetics and safety/tolerability over a range of doses. Drugs that are being repurposed from other indications and are generally recognized as safe may not require these Phase 1 studies, but usually do require preliminary human studies to establish penetration into the central nervous system and/or target engagement. These are sometimes referred to as Phase 1b studies. Only when the appropriate Phase 1 studies are successfully completed can a larger, Phase 2 trial be approved.
Applications for this program will be accepted from academic investigators and small companies with lead candidate therapeutic agents that require early stage testing prior to POC Phase 2 or 3 efficacy studies, or with lead therapeutic agents that have already established human safety data and require a small-scale pilot proof-of-mechanism (POM) study to begin proving the scientific concept in humans. This award will support Phase 1 studies or pilot small-scale Phase 2a studies for repurposed drugs in normal individuals or individuals with preclinical or symptomatic Alzheimer’s disease (i.e., early human studies to set the stage for efficacy studies), including single- and multiple-dose studies to establish safety, brain penetration and/or target engagement and POM in preparation for larger POC trials. In addition, proposals may be considered that are POC to validate biological markers of disease progression in a clinical trial environment.
Each award is limited to $600,000 (direct and indirect costs) for two or three years. All proposals must have a clear focus on Alzheimer’s disease and related disorders and be translational in nature. Letters of intent must be received by 5 p.m. EST June 27, 2014, and must address the RFA both in scope and location.
Full program announcement and more details are available at alz.org/grants or by emailing [email protected]. This program is made possible through the generous funding from the 2014 Part the Cloud, benefiting the Alzheimer’s Association.
Dr. Snyder is Director of Medical and Scientific Operations at the Alzheimer’s Association. She oversees the Association’s International Research Grant Program, the mechanism through which the Association funds research applications. In addition to ensuring the smooth review of applications and distribution of awards to successful applications, she is responsible for the dissemination of results and ongoing investigations to a wide range of audiences.
She also manages a collaborative project with the National Institute on Aging of the National Institutes of Health to develop an International Alzheimer’s Disease Research Portfolio – using common language to describe funded research to enable the integration and comparative analysis of Alzheimer’s research funding from public and private organizations from around the world.
Dr. Snyder received her Ph.D. from Loyola University Chicago Stritch School of Medicine and her B.A. in Biology and Religious Studies from the University of Virginia. Since graduating from Stritch, she completed a postdoctoral fellowship in the Neurobiology Program at Children’s Memorial Research Center, affiliated with Northwestern University in Chicago.
The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk or dementia through the promotion of brain health. Our vision is a world without Alzheimer’s disease. www.alz.org