# An Integrated Drug Discovery Platform for Neurodevelopmental Disorders Using Standardized Self-Organizing Human Cerebroids

> **NIH NIH R44** · RUMI SCIENTIFIC, INC. · 2024 · $1,006,032

## Abstract

Project Summary
Autism Spectrum Disorders (ASDs) are extremely prevalent and have no cure. These diseases
affect the way neurons are specified and communicate with one another. In this project, we will
create an in vitro tool to reveal monogenic ASD phenotypes at the level of neuronal assemblies
mimicking physiological and pathological neuronal network development in the human cortex, by
creating self-organized networks of forebrain neurons on micropattern substrates: the cerebroids.
Compared to existing techniques, our platform is extremely standardized and uses tools from the
world of artificial intelligence to detect subtle morphological differences associated with the
disease state. This uniquely allows us to test large numbers of molecules to discover new
therapeutics. This project brings together an interdisciplinary team to develop an innovative
solution for a problem that has no solution yet: the discovery of therapeutics for ASDs. Based on
our preliminary data showing that neuronal progenitors can self-organize on micropattern
substrates and give rise to consistent mutant phenotypes across banks of patient derived cells,
we will first optimize our protocols and characterize the normal developmental time course of
human cerebroids. This will create a baseline for normal development that will then be used to
measure the pathogenic effects of highly penetrants mutations associated to five monogenic
forms of ASDs associated with: ADNP, DDX3X, FOXP1, FOXG1 and SHANK3, creating a rich
ASD-focused pipeline together with key patient led research foundations. Next, we will develop
methods for probing neuronal communication within cerebroids based on live imaging of calcium
reporters. This will allow the study of neuronal cell development and interactions at the level of a
standardized micro-tissue and bridge an important gap in our ability to model and precisely
quantify human neural networks. Finally, we will engage in a drug discovery project for small
molecule therapeutics for one ASD gene using, as a primary screen, deep learning mediated
morphological readouts of phenotypic reversal, and subsequent evaluation of the hits at the level
of neuronal communication with a live imaging strategy. The successful molecules will be strong
therapeutic candidates that will eventually be moved towards evaluation in mice models. At the
technical level, this research is impactful as it realizes the dream of placing synthetic human micro
tissues at the center of the drug discovery process. This will have long- lasting consequences in
the way drugs will be found for neurological disorders in a filed currently characterized by large
investments yet many failures. New tools lead to new discoveries - and our platform provides a
unique opportunity to find new therapeutics in synthetic neural organoids for ASDs.

## Key facts

- **NIH application ID:** 10921822
- **Project number:** 1R44MH136894-01
- **Recipient organization:** RUMI SCIENTIFIC, INC.
- **Principal Investigator:** Fred Etoc
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,006,032
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10921822

## Citation

> US National Institutes of Health, RePORTER application 10921822, An Integrated Drug Discovery Platform for Neurodevelopmental Disorders Using Standardized Self-Organizing Human Cerebroids (1R44MH136894-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10921822. Licensed CC0.

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