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Testing Lifespan/Healthspan-Extension Interventions in the Models of Alzheimer’s Disease (AD/ADRD) (R41/R42 Clinical Trial Not Allowed)


  1. Section I. Funding Opportunity Description

    The Small Business Technology Transfer (STTR) program is a program that expands funding opportunities in the federal innovation research and development (R&D) arena. Central to the program is expansion of the public/private sector partnership to include the joint venture opportunities for small businesses and nonprofit research institutions. The unique feature of the STTR program is the requirement for the small business to formally collaborate with a research institution in Phase I and Phase II. STTR's most important role is to bridge the gap between performance of basic science and commercialization of resulting innovations.

    In the United States, more than 5 million people suffer from Alzheimer's disease (AD) and Alzheimer's-disease-related dementias (ADRD). By 2050 this number is forecasted to rise to more than 15 million. The care and treatment of patients with AD/ADRD is estimated to cost approximately $200 billion each year. As part of the National Institute on Aging's (NIA) strategic plan to support the development of innovative strategies and therapies to prevent, diagnose, and treat AD/ADRD, this new Funding Opportunity Announcement (FOA) intends to use Small Business Technology Transfer Program (STTR) to encourage research and development of commercial pharmaceutical interventions, based on those known to extend lifespan and/or healthspan, to prevent, treat, and/or slow the progression of symptoms associated with Alzheimer's disease (AD) and or Alzheimer's disease related dementia (ADRD) in human cells and/or tissues, in-vitro models, and/or non-human animals. 

    In the past three decades, research on the biology of aging has acquired a broad knowledge about the underlying mechanisms of aging and longevity.  These studies have led to a quite comprehensive understanding of the cellular mechanisms of aging, including changes in many genes, pathways, important cellular components, and biomolecules involved in the aging process.  The work conducted so far has been done mostly in model organisms (from yeast to non-human primate), and has demonstrated that these lifespan-regulating pathways are shared across species. Along with these mechanistic studies, considerable research efforts have been devoted to test various interventions for their ability to extend lifespan and/or healthspan in animal models.

    To advance the goal of identifying pharmaceutical lead compounds, combat the variability of lifespan assays and establish rigorous testing methodology, NIA started the Intervention Testing Program (ITP) ( fourteen years ago to test compounds/diets purported to benefit healthy aging using a genetically heterogeneous mouse model, with lifespan as the primary read-out and healthspan measurements as secondary readout. Some compounds tested in ITP have shown significant extension of median lifespan, including aspirin, rapamycin, 17α-estradiol, acarbose, nordihydroguaiaretic acid (NDGA), and protandim. In 2014, NIA also started the Caenorhabditis Intervention Testing Program (CITP) (, which aims to identify pharmacological interventions that increase lifespan and/or healthspan in a robust manner using a collection of natural variant isolates of Caenorhabditis.

    Success in this kind of approach is likely to be derived from studies that target conserved pathways and exploit the complementary advantages of multiple model systems. In fact, in the past two decades, many pharmaceutical interventions have been identified that effectively extend lifespan in animal models, including rapamycin, resveratrol, some senolytics, and ThioflavinT.   ThioflavinT is also known to suppress the aggregation and toxicity associated with the expression of a human neurotoxic peptide (AB 1-40) and promotes protein homeostasis. Some of these interventions have been rigorously tested and confirmed by ITP or CITP in mice and worms respectively. Aging is a major risk factor for most chronic diseases and degenerative conditions in adults, including Alzheimer’s disease. By this reasoning, those interventions that can slow aging should be effective in preventing or treating AD/ADRD. Despite a strong rationale and the rapid progress in discovering anti-aging interventions in animal models, most of these lifespan/healthspan extension interventions have never been tested for their potential benefits in AD/ADRD models. This FOA aims to encourage small business community to test these interventions, mostly pharmaceutical compounds, in AD/ADRD models for their effects on the activities of AD/ADRD genetic alleles, their cellular properties, and cognitive/behavioral phenotypes that are related to the progression and pathogenesis of AD/ADRD.

    In conclusion, this STTR FOA is intended to encourage the development and commercialization of pharmaceutical compounds and/or other interventions, that have been shown to extend lifespan and/or healthspan in animal models, to prevent, treat, or slow the progression of symptoms or phenotypes associated with AD/ADRD in human cells and/or tissues, in-vitro models, or non-human animal models. The lifespan/healthspan extension interventions covered by this FOA are not limited to those tested in the ITP or the CITP.

    Examples of topics that might be supported by this FOA include but are not limited to:

    • Development of assays that can test the effects of lifespan/healthspan extension compounds on activities of AD/ADRD genetic alleles or proteins;
    • Testing of the effects of lifespan/healthspan extension compounds on properties of cells with AD/ADRD genetic alleles;
    • Testing of the effects of lifespan/healthspan extension compounds in AD/ADRD invertebrate models for phenotypes related to AD/ADRD;
    • Testing of the effects of lifespan/healthspan extension compounds in AD/ADRD rodents or other vertebrate non-human animal models for phenotypes or symptoms related to AD/ADRD; and
    • Testing of the effects of lifespan/healthspan extension compounds in AD/ADRD human iPSCs or tissue culture systems (including 3-D culture and organoid) for their properties related to AD/ADRD or AD/ADRD genetic alleles.

    See Section VIII. Other Information for award authorities and regulations.

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