# High-throughput testing of anti-aging and FDA approved drugs in genetically diverse invertebrate Alzheimer's models

> **NIH NIH R43** · NEMALIFE INC. · 2021 · $348,285

## Abstract

Project Abstract
Alzheimer’s disease (AD) is the leading cause of dementia, with incidence on the rise—clearly central to a
global health crisis. Clinical symptoms often manifest as a progressive decline in cognitive ability and memory
impairment but eventually leads to loss of control of vital functions. AD is a slow-developing neurodegenerative
disease for which age is the leading risk factor indicating that aging interventions and lifespan extending drugs
might be AD-effective. Although, hundreds of anti-aging compounds have been identified, very few of these
compounds have been evaluated on animal models of AD. Our premise is that the AD models of the nematode
C. elegans have much to contribute to the identification of lead candidate drugs that improve neuronal aging
and protect against proteostasis disease. We propose to use a novel high-throughput technology to screen
many FDA approved drugs and anti-aging compounds in C. elegans enabling us to test longevity-promoting
compounds that will include a subset with potent effects against AD-related toxicity.
AIM 1: Perform a screen on C. elegans AD models with lifespan-extension and FDA-approved drugs. In
this aim, we plan to screen 300 anti-aging compounds and 200 FDA-approved drugs that target the hallmarks
of aging on C. elegans AD models. The screen capitalizes on NemaLife’s high throughput screening platform
with phenotypic end-points of mobility declines and survival. Hits will be confirmed by in vivo imaging of
aggregates. This task will generate a compound lead series for AD drug development pipeline.
AIM 2. Prioritize lead candidates by addressing critical gaps in preclinical AD drug discovery. Robust
translation of drugs requires testing lead series with genetically diverse AD strains and also developing
combination therapy to target multiple AD pathways. We will generate recombinant C. elegans strains to
address genetic diversity in AD and plan to screen the most promising compounds and determine if
interventions administered at early adult or late adult (onset of symptoms) stages are effective. Finally, a proof-
of-principle combination study that involves compounds targeting hallmarks of aging will be piloted against the
AD models. This multi-prong approach is expected to de-risk drug failure in mammalian AD models.
In summary, we will use a novel NemaLife technology to identify a subset of pharmacological longevity
interventions will exert neuroprotection against AD-relevant stresses. The outcome will establish both
promising candidates for AD preclinical study and potentially clinical trials and a much-needed work-horse tool
in drug discovery that prioritizes compounds for human AD.

## Key facts

- **NIH application ID:** 10139953
- **Project number:** 1R43AG071142-01
- **Recipient organization:** NEMALIFE INC.
- **Principal Investigator:** Marton Toth
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $348,285
- **Award type:** 1
- **Project period:** 2021-01-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10139953

## Citation

> US National Institutes of Health, RePORTER application 10139953, High-throughput testing of anti-aging and FDA approved drugs in genetically diverse invertebrate Alzheimer's models (1R43AG071142-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10139953. Licensed CC0.

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