# A Drug Discovery Platform to Prioritize Development of Natural Product Neuromodulators for Treating Cognitive Impairment

> **NIH NIH R44** · SENSORIUM THERAPEUTICS INC · 2024 · $502,499

## Abstract

PROJECT SUMMARY
Mild Cognitive Impairment (MCI) is one of the earliest and most noticeable symptoms associated with
Alzheimer’s Disease (AD) and other AD Related Dementias (ADRD). There is no cure for ADRD, and
conventional treatments only target more disease stages. Notably, MCI associated with AD typically occurs after
AD biomarkers (related to β-amyloid and tau pathologies) are detectable in patients, creating a narrow window
prior to MCI-AD onset and diagnosis, termed preclinical AD, where interventions slowing MCI onset have the
potential to greatly improve patient quality of life and dramatically reduce costs of AD care at large. However,
developing pharmaceutical treatments for preclinical AD must meet high safety margins given the duration of
treatment, and past attempts have failed to show efficacy. Recently, approvals of antidepressants like ketamine
and brexanolone (both 2019) and the resurgence of psychedelic research has highlighted the power of
neuroplasticity modifiers – compounds driving the creation or modulation of synaptic connections within the brain
– for modifying neurological function to impact mental health. Engaging neuroplasticity mechanisms through
pharmacological means or holistic approaches (i.e. exercise & dietary changes) has been shown to positively
enhance cognition and memory. Notably, some of the most potent neuroplasticity modulators are Natural
Products (NPs) derived from medicinal plants and herbs used by humans for centuries. As such, NPs have been
the subject of numerous studies investigating their potential to improve cognition and progression to MCI in AD.
However, incomplete descriptions of NP molecular targets, mechanisms of action, stability, purity, potency and
bioavailability have largely prevented their development as clinical drug candidates. What’s more, the quantity
of known NPs found in botanical products numbers in the tens of thousands. To identify and develop
psychoactive natural products that impact neuroplasticity and can slow MCI onset, Sensorium Therapeutics is
expanding the capacity of their Biodynamic Discovery PlatformTM (BDP). Our novel BDPTM leverages AI-assisted
analysis of ethnobotanical data and medicinal chemistry coupled with in vitro high-throughput screening using
human iPSCs to provide an effective drug development pipeline for identifying novel NPs as MCI-AD treatments.
Our platform has already led to the identification of a leading natural product drug candidate for depression and
anxiety. Additionally, we have identified a class of botanically-derived alkaloid compounds that have favorable
CNS pharmacological profiles, excellent chemical and in vitro safety, and are linked to improving cognitive
function in humans. The overarching goal of this Fast Track proposal is to expand our BDPTM to include scalable
cellular/neuronal readouts of neuroplasticity while incorporating MCI-AD in vitro models (Phase I) and identify
and validate NP candidate efficacy for MCI-AD treatment (P...

## Key facts

- **NIH application ID:** 10821852
- **Project number:** 1R44AG085858-01
- **Recipient organization:** SENSORIUM THERAPEUTICS INC
- **Principal Investigator:** Jeffrey M. Brown
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $502,499
- **Award type:** 1
- **Project period:** 2023-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821852

## Citation

> US National Institutes of Health, RePORTER application 10821852, A Drug Discovery Platform to Prioritize Development of Natural Product Neuromodulators for Treating Cognitive Impairment (1R44AG085858-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10821852. Licensed CC0.

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