R35AG071734

Leadership in AD/ADRD Drug Discovery - Summary

This R35 leadership application is relevant to Milestone 6D of the goals/milestones of the NIH Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) Summits—"Initiate drug discovery efforts to develop novel therapeutic agents." Our overriding goal in this application is to support the infrastructure the PI is assembling for AD/ADRD drug discovery at Scripps Research, which will continue well after the award is over.

Our major planned milestone is aimed to inspire program building and create team building for AD/ADRD drug discovery using the very considerable institutional resources at Scripps Research and its Calibr Drug Discovery Center. We are also building one of the nation's top-ranked graduate school programs in drug discovery via our mentoring using the faculty of Scripps' #1/#2-ranked chemistry-biochemistry departments in the world.

As proof of feasibility, of the six currently FDA-approved medicines for AD, three were developed out of the PI, Dr. Lipton's laboratory. Via this R35 leadership application, Dr. Lipton will mentor others to develop AD/ADRD-related drugs acting at novel targets toward disease-modifying therapy. Specifically, Dr. Lipton will serve as research mentor for new investigators and early stage investigators (NI/ESI) in AD/ADRD drug discovery.

To date, virtually all AD/ADRD therapeutics evaluated in human clinical trials have so far failed to show disease-modifying effects for AD/ADRD. For example, the lack of significant efficacy in clinical trials with amyloid-beta (Ass)-centered therapeutics to date demands a new paradigm for the development of effective AD therapeutics. To overcome these significant gaps in knowledge and to advance therapies, improvements in the models and strategies by which AD/ADRD researchers function and execute need to occur.

One solution to this challenge is to unite the best basic scientists with training in neuroscience, structural biology, bioinformatics, and computational biology, with equally expert teams in the pharmaceutical industry trained in high-throughput screening, assay development, medicinal chemistry, chemical biology, and pharmacology. With a collective and harmonized team along with significant mentoring efforts for junior faculty (NI/ESI), the PI, Dr. Lipton, has initiated three major efforts to address this unmet medical need, which will be carried out under the auspices of the current R35 leadership award application:

1. Investigation, identification, and characterization of potential AD/ADRD therapeutic targets in the context of the central pathophysiological processes in AD/ADRD.

2. Execution of drug discovery campaigns to develop investigational new drug (IND) clinical candidates iteratively with the target elucidation efforts, while building upon Scripps Drug Discovery infrastructure to accomplish this.

3. Continue to mentor junior faculty and build a world-class graduate school around the chemical biology of drug design for AD/ADRD at Scripps (currently ranked #2 by US News for biochemistry).

Scripps Research Institute

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

La Jolla, California 920371000 United States

Single Zip Code

Leadership Award for Alzheimer's Disease and Related Dementias Research (R35 Clinical Trial Not Allowed) (RFA-AG-21-007)

Amendment Since initial award the total obligations have increased 407% from $1,062,600 to $5,389,748.