# Administrative Supplement for 1R01AG059008-01: Requested for investigational drug expenses

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $402,379

## Abstract

ABSTRACT
The vast majority of therapeutic interventions targeting Alzheimer's disease (AD) until now have focused on
monotherapies to alter a single neuropathology. Unfortunately, all these approaches have failed to meet the
clinical endpoint of significantly slowing or reversing cognitive decline in AD subjects. This emphasizes the
urgent need for novel therapeutic interventions to reduce several AD neuropathologies simultaneously.
 Inflammation is pervasive to many neurological disorders, yet no clinical trial has demonstrated the efficacy
of anti-inflammatory agents for AD. Our research group is particularly interested in drugs that lower both
systemic and central inflammation aiming at preventing or slowing down the clinical progression of AD. Our
most promising compound is the immunomodulator, anti-cancer agent lenalidomide, which is one of the very
few pleiotropic agents that both lowers the expression of pro-inflammatory (e.g. TNFα, IL-6, IL-8), and
increases the expression of anti-inflammatory cytokines (e.g. IL-10), to modulate both innate and adaptive
immune responses.
 Capitalizing on our experience from a previous clinical trial with an analog and our animal data, in the
current project we aim to test the central hypothesis that lenalidomide reduces AD-associated
neuroinflammation and neuropathologies, which might result in improved cognitive performances. For this, we
designed a Phase Ib-IIa, proof-of-mechanism, placebo-controlled clinical study on single and multiple domain
amnestic MCI subjects administered 10 mg/day lenalidomide for 12 months. Because lenalidomide has never
been tested in the context of AD, we will monitor carefully the safety and tolerability in MCI patients. To
demonstrate the engagement of lenalidomide in study subjects, we will measure inflammatory markers in the
periphery every 3 months. We will measure cognitive performance via MCI-sensitive tests. In addition, we will
assess target engagement (CSF markers) at the completion of dosing. This is highly significant because, if
successful, lenalidomide will become one of the very few compounds capable of lowering several
neuropathological features associated with AD. Furthermore, the major advantage of lenalidomide is that the
drug I already FDA-approved for cancer treatment, thus it could rapidly be repurposed in a Phase IIb study.

## Key facts

- **NIH application ID:** 10166454
- **Project number:** 3R01AG059008-02S1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Boris Decourt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,379
- **Award type:** 3
- **Project period:** 2018-09-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166454

## Citation

> US National Institutes of Health, RePORTER application 10166454, Administrative Supplement for 1R01AG059008-01: Requested for investigational drug expenses (3R01AG059008-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10166454. Licensed CC0.

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